Medicament dispenser

ABSTRACT

There is provided a medicament dispenser for containing plural elongate form medicament carriers, each having multiple distinct medicament dose portions carried thereby, the dispenser having a housing of generally non-circular form, and within said housing a dispensing mechanism for dispensing the distinct medicament dose portions carried by each of said plural medicament carriers. The mechanism comprises at least one receiving station for receiving each of the plural medicament carriers; a release for releasing in combination a distinct medicament dose portion from each of the plural medicament carriers on receipt thereof by said receiving station; an outlet, positioned to be in communication with the distinct medicament dose portions releasable by said release; and at least one indexer for individually indexing the distinct medicament dose portions of each of the plural medicament carriers. The dispenser contains plural elongate form medicament carriers, each having multiple distinct dose portions carried thereby. At least one of said medicament carriers has the form of a continuous loop.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is filed pursuant to 35 U.S.C. §371 as a United StatesNational Phase Application of International Application No.PCT/EP2004/008235 filed 21 Jul. 2004, which claims priority from GB0317374.7 filed 24 Jul. 2003.

TECHNICAL FIELD

The present invention relates to a medicament dispenser for dispensingmedicament. The invention particularly relates to a dispenser for use indispensing medicament in powder or tablet form.

BACKGROUND OF THE INVENTION

The use of inhalation devices in the administration of medicaments, forexample in bronchodilation therapy is well known. Such devices generallycomprise a body or housing within which a medicament carrier is located.Known inhalation devices include those in which the medicament carrieris a blister strip containing a number of discrete doses of powderedmedicament. Such devices usually contain a mechanism of accessing thesedoses, usually comprising either piercing means or means to peel a lidsheet away from a base sheet. The powdered medicament can then beaccessed and inhaled. Such a mechanism may also be used for dispensingmedicament in tablet form wherein peeling away the lid sheet from thebase sheet reveals a tablet for removal and subsequent consumption.

Therapies involving combinations of different and complementary activemedicaments are known. These can be administered either as distinctcombination (i.e. multi-active) medicament products, which comprise adefined mixture of each component medicament, or as groups of singleactive medicament products, which are designed to be taken incombination or sequentially. Whilst combination products offer addedconvenience for the patient, certain medicament actives are difficult toformulate as distinct combination products. For example, the actives mayinteract chemically with each other in an undesirable way whenformulated together.

It is thus, desirable in certain circumstances, to have a medicamentdispenser that separately (i.e. in isolated fashion) contains eachactive component (or mixture thereof) of a combination product, butwhich enables the delivery of a combined dose in response to a minimumnumber of patient actions. In particular, it is desirable that allactive components of the combined dose are delivered to the patient in asingle, combined dose in response to a single patient dosing action. Forexample, it is desirable that a combination inhaled medicament productbe delivered in response to a single actuation of an inhaler, even wherethe active components of that combined product are separately storedwithin the inhaler device.

A particularly effective way to meet the above described desiderata isprovided by a medicament dispenser which comprises plural, separateelongate form medicament carriers (e.g. strip or continuous loop formblister packs), each containing in isolated fashion, a differentmedicament active (or mixture thereof), wherein the dispenser enablesrelease of the medicament actives from each separate blister pack toprovide a combined dose for administration to a patient.

Such a medicament dispenser for use with plural elongate form medicamentcarriers, each having multiple distinct medicament dose portions carriedthereby, typically comprises a dispensing mechanism for sequentiallydispensing the distinct medicament dose portions carried by each of saidplural medicament carriers. The dispensing mechanism suitably comprisesa receiving station for receiving each of the plural medicamentcarriers; a release for releasing a distinct medicament dose portionfrom each of the plural medicament carriers on receipt thereof by saidreceiving station; an outlet, positioned to be in communication with thedistinct medicament dose portions releasable by said release; and anindexer for individually indexing the distinct medicament dose portionsof each of the plural medicament carriers. A medicament dispenser ofthis type has been described in Applicant's previous PCT application no.WO 03/061743.

The Applicant has now found that in providing a medicament dispenser ofthis type a number of practical problems and design challenges areencountered.

One problem is that of providing a dispenser device that is able toaccommodate the plural medicament carriers, but is of sufficiently smalloverall size that it is conveniently portable (e.g. in the pocket or bagof a patient) and amenable to discrete use, by the patient. Herein, theApplicant describes a number of ways to ameliorate the problem of‘saving space’ within the dispenser including the use of medicamentcarriers in continuous loop form housed within a non-circular formhousing.

Another problem is that of providing a dispenser device, in which thedistinct medicament dose portions of each of the plural medicamentcarriers may be indexed or accessed without the need for the user toapply undue indexing or accessing force. Particular challenges are facedwhen the plural medicament carriers are required to be moved through thedispenser device for indexing/accessing thereof, and where theindexing/accessing action is coupled (e.g. moving peelable blisterstrips through the dispenser device to both index a particular blisteron each strip and peelably access that blister). The Applicant hereindescribes a number of ways to ameliorate the problem of ‘reducing userforce’ required for actuation.

Another problem is that of providing a dispenser device that is able toaccommodate the plural medicament carriers and enable efficientindexing/accessing, but which may be configured in an overall form thatis ergonomically suitable for patient usage.

Another problem is that of providing a dispenser device that is readilyactuable by a conveniently located actuation lever.

Various additional and subsidiary problems are also described herein,and means for addressing them also described.

SUMMARY OF THE INVENTION

According to one aspect of the present invention there is provided amedicament dispenser for containing plural elongate form medicamentcarriers, each having multiple distinct medicament dose portions carriedthereby, said dispenser having a housing of generally non-circular form,and within said housing a dispensing mechanism for dispensing thedistinct medicament dose portions carried by each of said pluralmedicament carriers, said mechanism comprising,

a) at least one receiving station for receiving each of the pluralmedicament carriers;

b) a release for releasing in combination a distinct medicament doseportion from each of the plural medicament carriers on receipt thereofby said receiving station;

c) an outlet, positioned to be in communication with the distinctmedicament dose portions releasable by said release; and

d) at least one indexer for individually indexing the distinctmedicament dose portions of each of the plural medicament carriers,

wherein said dispenser contains plural elongate form medicamentcarriers, each having multiple distinct dose portions carried therebyand at least one of said medicament carriers has the form of acontinuous loop.

In one aspect, all of the medicament carriers have the form of acontinuous loop.

The housing of the dispenser suitably defines a shell for enclosing thedispensing mechanism and medicament carriers. The housing is ofgenerally non-circular form.

Suitably, the housing has an elongate form. In one aspect, the housingdefines a generally ovoid profile (i.e. it has an ovular form), whichmay be a flat ovoid.

In one aspect, the housing is arranged to be foldable about an axis.Suitably, the housing is hinged about a conventional or ‘living hinge’to facilitate such folding. In the folded form, the housing is generallymore compact such as to facilitate carrying of the dispenser in thepocket of a user.

The plural elongate form medicament carriers may adopt essentiallysuitable profile within the dispenser. Preferably, the housing is shapedsuch as to define a profile that facilitates space-efficient arrangementof the carriers within the housing.

In one aspect, at least one of the plural elongate form medicamentcarriers adopts a C-shaped profile. In another aspect, at least one ofthe plural elongate form medicament carriers adopts an S-shaped profile.In a further aspect, at least one of the plural elongate form medicamentcarriers adopts a caterpillar track profile (e.g. like the caterpillartrack on a military tank vehicle).

In combination, the distinct medicament dose portions releasable fromeach of the plural medicament carriers comprise a defined dose ofcombination product. That is to say, that when combined together (e.g.on release) the distinct active medicament dose portions form a singledose of a ‘multi-active’ medicament treatment.

The medicament dispenser is designed to receive plural elongate formmedicament carriers. Preferably, the medicament dispenser is designed toreceive from two to four such elongate form medicament carriers, morepreferably two such carriers. For flexibility it is also envisaged thatthe medicament dispenser may be used with only one medicament carrier,the other parts of the dispenser mechanism being essentially redundantin this usage pattern.

Each medicament carrier has multiple distinct dose portions carriedthereby. The distinct dose portions are typically arranged in spacedfashion, more preferably in progressive arrangement (e.g. seriesprogression) on the carrier such that each dose portion is separatelyaccessible.

The term medicament carrier herein is used to define any suitable formof carrier. Suitably, each elongate form medicament carrier is in theform of a strip or tape, which may either have open ends or ends joinedup such as to form a continuous loop. In one preferred aspect, thecarrier has a blister pack form, but it could also, for example,comprise a carrier onto which medicament has been applied by anysuitable process including printing, painting and vacuum occlusion.

In one aspect, the medicament carrier comprises a blister pack inlaminate form. Suitably, the laminate comprises material selected fromthe group consisting of metal foil, organic polymeric material andpaper. Suitable metal foils include aluminium or tin foil having athickness of from 5 to 100 μm, preferably from 10 to 50 μm, such as 20to 30 μm. Suitable organic polymeric materials include polyethylene,polypropylene, polyvinyl chloride and polyethylene terephthalate.

Access to the medicament dose portions comprised within the pockets ofthe elongate strip form carrier is by any suitable access meansincluding tearing, piercing or peeling apart the relevant pockets.

One suitable blister pack form medicament carrier comprises a peelableblister strip. Suitably, the peelable blister strip comprises a basesheet in which blisters are formed to define pockets therein forcontaining distinct medicament dose portions and a lid sheet which ishermetically sealed to the base sheet except in the region of theblisters in such a manner that the lid sheet and the base sheet can bepeeled apart. The base and lid sheets are typically sealed to oneanother over their whole width except for the forward end portions wherethey are typically not sealed to one another at all. Thus, separate baseand lid sheet forward end portions are presented at the end of thestrip. The respective base and lid sheets are peelably separable fromeach other to (e.g. separately) release the contents of each pocket.

Suitably, the lid sheet comprises at least the following successivelayers: (a) paper; adhesively bonded to (b) polyester; adhesively bondedto (c) aluminium foil; that is coated with a heat seal lacquer forbonding to the base sheet. The thickness of each layer may be selectedaccording to the desired properties but is typically of the order offrom 5 to 200 micron, particularly from 10 to 50 micron.

Suitably, the base sheet comprises at least the following successivelayers: (a) oriented polyamide (OPA); adhesively bonded to (b) aluminiumfoil; adhesively bonded to (c) a third layer comprising a polymericmaterial (e.g. polyvinyl chloride).

Various known techniques can be employed to join the lid and base sheetand hence to seal the blisters of the peelable blister strip. Suchmethods include adhesive bonding, hot metal bonding, hot metal welding,radio frequency welding, laser welding, ultrasonic welding and hot barsealing. The lid sheet and base sheet of the peelable blister strip areparticularly sealable by ‘cold form’ sealing methods, which areconducted at lower temperatures than conventional heat sealing methods.Such ‘cold form’ sealing methods are of particular utility where themedicament or medicament formulation for containment within the blisteris heat sensitive (e.g. degrades or denatures on heating). Suitable‘cold form’ sealing methods are conducted at a temperature in the rangeof 150-250° C., more preferably, 210-240° C.

Each medicament carrier has multiple distinct (i.e. separate) medicamentdose portions carried thereby. The term ‘dose portion’ is employedbecause in the context of the invention the distinct ‘portions’ arebrought together to form a combination (i.e. multi-active) product dose.in one aspect, each ‘dose portion’ comprises a single active (i.e.mono-active) medicament component. Each mono-active component istherefore brought together only at the time of release to form theoverall combination product.

In another aspect, one or more of the ‘dose portions’ comprise pluralactive medicament components (e.g. as a formulated mixture thereof).Typically, these plural components will be ‘co-formulation compatible’wherein that term is used to mean compatible in the sense of beingamenable to co-formulation, perhaps even displaying synergeticco-formulation characteristics.

In one particular aspect, a first elongate form medicament carrier hasmultiple distinct mono-active medicament dose portions carried therebyand a second elongate form medicament carrier has multiple distinctplural-active (particularly, bi-active dose portions i.e. comprising twoactive components) medicament dose portions carried thereby. Incombination, the mono-active and plural-active medicament componentscomprise a defined combination product. That is to say, that whencombined together the distinct mono- and bi-active medicament doseportions released by actuation of the dispenser form a dose of a‘multi-active’ medicament treatment.

In one aspect, each of the elongate form medicament carriers is sizedand shaped to carry equivalent dose portions, that is to say eachcarrier is suitable for carrying dose portions of equivalent dose volumeor dose weight. In one particular example, each medicament carrier of abi-carrier dispenser is arranged to carry plural 12 mg (or 25 mg) doseportions.

In another aspect, each of the elongate form medicament carriers issized and shaped to carry non-equivalent dose portions, that is to sayeach carrier is arranged to carry dose portions of non-equivalent dosevolume or dose weight to the other. In one specific example, a firstmedicament carrier of a bi-carrier dispenser is arranged to carry plural12 mg dose portions and the second carrier thereof is arranged to carry25 mg dose portions.

In one aspect, the multiple distinct dose portions are provided to eachcarrier in uniform series. In particular, the spacing (i.e. pitch)between each dose portion is uniform throughout the series. In otheraspects however, the spacing (i.e. pitch) may vary throughout the series(i.e. be non-uniform). In specific examples, the pitch may progressivelydecrease or progressively increase throughout the series. Such variationmay in aspects, be required to compensate for non-uniform indexing bythe carrier indexing and/or advancement mechanism of a particulardispenser.

In one aspect, the spacing (i.e. pitch) between each dose portion isequivalent for each carrier of the dispenser. That is to say, eachmedicament carrier is equivalently pitched. In other aspects, thespacing between each dose portion is non-equivalent for each carrier ofthe dispenser. Such variation of the spacing (i.e. pitch) from carrierto carrier can be used to enable flexibility in (combination) dosagepatterns.

In one particular example, the spacing (i.e. pitch) of a first carrieris arranged to be half that of a second carrier. This arrangement isbeneficially employed where the dose interval (i.e. time between doses)of the medicament carried by the first carrier is twice that of themedicament carrier by the second carrier (e.g. in a twice daily/oncedaily type dosage regime).

The plural elongate form medicament carriers may be provided to thedispenser in any suitable configuration. One suitable configuration isthe ‘side-by-side’ configuration, in which for example, two carriers(e.g. two coiled blister strips) are arranged to lie in sidewaysalignment with each other in the dispenser. Another suitableconfiguration is the ‘double-decker’ configuration, in which forexample, two carriers (e.g. two coiled blister strips sharing the samecoiling axis) are arranged to lay one on top of each other in thedispenser.

The plural carriers are typically provided to the dispenser as separateentities. Alternative embodiments are however, envisaged in which theseparate plural elongate carriers are joined together in someappropriate fashion. Thus, for example in a variation of an embodimentcomprising two separate elongate strip form carriers each carryingmultiple distinct medicament dose portions arranged in series along therespective strip and mountable in the dispenser in ‘double-decker’configuration there might be provided a single strip comprising twoseparate series of multiple distinct medicament dose portions arrangedin ‘double decker’ configuration (i.e. parallel to each other) as if thetwo strips of the first embodiment had simply been joined together alongadjoining elongate sides thereof.

In a particular ‘joined together’ configuration, two elongate strip formcarriers are arranged in ‘back-to-back’ configuration (i.e. one stripbacks onto the other with the pockets of each facing outwards). In thisembodiment, the ‘back-to-back’ conjoined strip typically has pocketsarranged to alternate—one on its first side, then one on the other side.It will be appreciated that when so joined together, each component foilstrip of the conjoined whole effectively acts as a ‘lid foil’ for theother.

In one aspect, the elongate form carrier is arranged to have acontinuous loop form such as may be achieved by joining the lead end ofthe strip to the tail end. All suitable methods of joining areenvisaged, including adhesive bonding, hot metal bonding, hot metalwelding, radio frequency welding, laser welding, ultrasonic welding andhot bar sealing. The loop may be linearly formed or it may be formed asa Mobius strip.

In a particular aspect where the elongate form carrier is in the form ofa peelable strip, the base sheet is formed as a continuous loop. Invariations, the lid sheet, which forms a peelable sealing lid to thebase sheet, may either have continuous loop or non-continuous loop form.

Hybrid configurations are also envisaged, in which one or more elongatecarriers are in the form of an open strip (i.e. with unjoined ends) andone or more further elongate carriers is in the form of a continuousloop (e.g. formed by joining together the lead and tail ends of an openstrip).

The dispenser has a dispensing mechanism for dispensing the distinctmedicament dose portions carried by each of said plural medicamentcarriers for administration as a single, combination product dose by thepatient.

In aspects, some or all components of the dispensing mechanism arecommon for each of the medicament carriers. The advantage of havingcommon components is that the number of separate parts in the dispensermay be reduced.

In other aspects, the action of those components that are not common mayin aspects be suitably coupled. Coupling is achieved by any suitablefashion including mechanical linkages (e.g. co-gearing or via the use ofcoupling arms/rods) or electromechanical coupling controls. Theadvantage of coupling is that the indexing/advancement of eachmedicament carrier may be achieved in coupled fashion.

In other aspects, most or even all of the components of the dispensingmechanism are distinct. In one particular aspect, the dispenser isarranged such that each of the plural medicament carriers can beindexed/advanced separately thereby providing the opportunity forcomplex dosing patterns in which any combination, or indeed any one, ofthe plural strips may be accessed. Where separate indexing/advancementis envisaged separate actuation means (e.g. levers or buttons) may beprovided to the dispenser to enable separate actuation thereof.

The dispensing mechanism herein comprises a receiving station forreceiving each of the plural medicament carriers. Embodiments areenvisaged both in which there is a single receiving station which iscapable of receiving plural medicament carriers and also those in whicheach medicament carrier is received by a distinct (i.e. individual)receiving station. In the latter case, the individual receiving stationsmay either be coupled or not.

The dispensing mechanism further comprises a release for releasing adistinct medicament dose portion from each of the plural medicamentcarriers on its receipt by the receiving station. The release can haveany suitable form. Where the elongate carrier is in the form of ablister pack, the release may for example, comprise means to rupture,puncture, tear or otherwise access the blister. In a particularpreferred aspect, where the medicament carrier is in the form of apeelable blister strip the release comprises means for peeling apart theblister strip. In one aspect herein, each blister strip is peeled apartabout a defined beak or wedge form feature of the dispenser.

An outlet is positioned to be in communication with the distinctmedicament dose portions releasable by said a release to enable theirdispensing to the patient. The outlet may have any suitable form. In oneaspect, it has the form of a mouthpiece. In another aspect, it has theform of a nozzle for insertion into the nasal cavity of a patient.

The outlet is preferably a single outlet, which communicates with all ofthe distinct medicament dose portions on their release by said release.Communication is for example, via a common air channelling means (e.g.formed as an air-pipe or common manifold). The patient may thereforebreathe in through a single outlet, and that breath be transferredthrough the common air channelling means to (all of) the releasedmedicament dose portions, thereby enabling their inhalation as acombined product. The outlet and/or channelling device may be shaped toencourage mixing of drug as a result of the airflow created byinhalation by the patient. For example, baffles or other mechanical aidsto mixing may be incorporated. Venturi channelling of the airflow isalso envisaged in embodiments. Helical form channels are envisaged.

The outlet is generally shaped to assist efficient docking with eitherthe mouth or the nasal cavity of the patient. In aspects, shaping may beprovided to promote good lip seal (e.g. transverse mouthpiece form) anduser tongue interaction with the mouthpiece.

The mechanism also comprises an indexer for indexing (e.g. individually)the distinct medicament dose portions of each of the plural medicamentcarriers. Said indexing typically happens in sequential fashion, forexample accessing dose portions sequentially arranged in series alongthe length of the elongate carrier. The indexing of each carrier may bearranged to occur in coupled fashion, that is to say each is indexedconcurrently.

In a preferred aspect, the medicament carrier comprises a peelableblister strip. In this aspect, the release suitably comprises a peelerfor peeling apart a base sheet and lid sheet of each peelable strip toopen a pocket. Suitably, the peeler includes lid driver for pullingapart a lid sheet from a base sheet of a pocket that has been receivedat the opening station.

Preferably, there is provided a medicament dispenser for use with pluralblister strip form medicament carriers, each having multiple distinctpockets for containing medicament dose portions, wherein said pocketsare spaced along the length of and defined between two peelable sheetssecured to each other, said dispenser having a dispensing mechanism fordispensing the medicament dose portions contained within said pluralmedicament carriers, said mechanism comprising,

a) an opening station for receiving a pocket of each of said medicamentcarriers;

b) a peeler positioned to engage a base sheet and a lid sheet of apocket which has been received in said opening station for peeling apartsuch a base sheet and lid sheet, to open such a pocket;

c) an outlet, positioned to be in communication with an opened pocketthrough which a user can access a medicament dose portion from such anopened pocket; and

d) an indexer for individually indexing the distinct pockets of each ofthe plural medicament carriers.

In accord with the present invention, the medicament dispenser includesone or more of the improvement features described herein.

In one aspect, a common opening station is provided for receiving apocket of each of said medicament carriers. In another aspect, distinctopening stations are provided for receiving a pocket of each medicamentcarrier. Suitably, the distinct opening stations are linked by acommunicating passageway or other means for enabling the coming togetherof the separately released medicaments.

Generally, the opening station(s) are located at a fixed position withinthe dispenser. In one aspect however, the opening station(s) are movablewithin the dispenser. The positioning of the opening station(s) maytherefore be varied during the course of operation of the dispenser e.g.to act as a compensating means to ensure uniform accessing of pocketsover the entire length of a strip form medicament carrier.

In one aspect, each movable opening station comprises a chamber (e.g. ofcruciform shape) that in use, moves to locate adjacent respective openedleading pockets of each blister strip. The chamber is suitably providedto a carrier (e.g. bobbin-shaped) that is movably mountable within thedispenser e.g. along a sprung axis.

In the dispenser, each peelable strip form medicament carrier is actedon by a peeler (i.e. peeling means). The peeler engages a base sheet anda lid sheet of a pocket that has been received at the opening station(s)for peeling apart the base sheet and lid sheet to open a pocket. In oneaspect, each peelable strip form medicament carrier is acted on bycommon peeler. In other aspects, each peelable strip is acted on by itsown (i.e. separate) peeler.

Suitably, the peeler includes a lid driver for providing pulling forceto a lid sheet and a peel surface about which the lid sheet is pulled,these features in combination acting such as to pull apart a lid sheetand a base sheet of a pocket (e.g. on receipt at the opening station).

The lid driver may have many forms, as described herein. The peelsurface about which the lid sheet is pulled typically comprises adefined beak or wedge form feature of the dispenser. It will beappreciated that the peel surface and lid driver will be located withinthe device to optimise the peeling force experienced by the peelablestrip.

In one aspect, the lid driver comprises a wheel on which the lid sheetis wound up, said wheel having a effective winding surface which remainsapproximately constant when tension in the lid sheet increases. In oneaspect, this is achievable by fashioning the lid driver in ‘collapsiblewheel’ form wherein the wheel collapses (i.e. the diameter of the wheelitself decreases) as lid sheet becomes wound around it to give it anoverall approximately constant effective winding diameter (as defined bythe diameter of the wheel and the strip wound around it). Suitably, said‘collapsible wheel’ comprises a plurality of resiliently flexible armseach extending there from at an angle with respect to a radius. Theleading end of the lid sheet is looped over one of said resilientlyflexible arms to secure the lid sheet to the wheel initially.

Alternatively, the lid driver comprises a wheel on which the lid sheetis wound up, said lid sheet wheel having an effective winding surface,the effective diameter of which increases after every use of thedispenser as the lid sheet winds around the wheel. Compensation meansare then provided to compensate for this increase, which would otherwiselead to a variation in the tension experienced by the lid sheet over itslength and hence a variation in its indexing over time.

In one aspect, there is provided a controller comprising means to limitthe extent of movement of said lid driver, in order to control thelength of medicament carrier peeled by said peeler. Hence, themedicament carrier is indexed by the same amount each time.

In another aspect, the dispenser comprises compensating means positionedbetween said opening station and said lid sheet wheel for reducing thelength of said lid sheet therebetween to compensate for any increase inthe diameter of the effective winding surface of the lid sheet wheelduring use of the dispenser.

Suitably, the compensating means takes the form of a flexible member.The flexible member may take the form of a flexible elongate arm aboutwhich the lid sheet is fed. The arm may flex inwards as tension in thelid sheet increases, and thus shorten the length of lid sheet betweenthe opening station and the lid driver.

Suitably, the flexible member is resilient so that on removal of tensionfrom the lid sheet, the flexible member returns to its rest position.Thus, the internal mechanism can be reloaded with a new medicamentcarrier after the used carrier is removed.

In one aspect, the compensating means takes the form of a spring thatreduces in length as tension increase in the lid sheet between theopening station and the lid driver. Typically a piston head is mountedon one end of the spring about which the lid sheet is fed. The other endof the spring may be fixed. As tension in the lid sheet increases thepiston is driven down onto the spring. Preferably, the compensatingmeans takes the form of a sprung-loaded tensioner.

In another aspect, the compensating means is positioned at the liddriver (e.g. lid sheet wheel). In particular, the compensating means actsuch as to vary (generally, to reduce) the drive functioncharacteristics of the lid driver to compensate for any increase in thediameter of the effective winding surface of the wheel during use of thedispenser. Thereby, the medicament carrier is uniformly indexed (i.e.typically indexed by the same length of strip) as a result of eachactuation of the dispensing mechanism, and the pocket opening action isalso experienced uniformly.

Suitably, the compensating means comprises a torsion spring positionedat the lid driver (e.g. lid sheet wheel). Suitably, the lid driver takesa hub form and the torsion spring is accommodated such as to provide atorsion hub drive, which may itself be driven by gears. In one aspect,in use, the torsion spring is initially tense and the tension reduces asthe lid driver receives lid sheet thereby also reducing its drive actionon later-received lid sheet (i.e. that lid sheet towards the tail end ofthe medicament carrier).

Suitably, the lid driver is in the form of a ‘vane hub’ and thecompensating means is provided by providing an inner wall of a drum formhub with multiple teeth and an insert locating within the drum, whereinthe insert defines a central spindle and protruding vane arms, the endsof which normally interact with the teeth on the inner wall of the drum.The insert is rotatable relative to the drum, but that rotation onlyoccurs when sufficient rotational force is applied to the drum toovercome the interaction of the teeth with the respective, resilientlyflexible vane arms. The nature of this interaction therefore defines aslipping (i.e. clutch) force, which must be overcome for free rotationof the insert relative to the drum to occur. In the absence of theslipping force the drum and insert 1 are fixed relative to each otherand rotatable as a single unit.

Suitably, the compensating means comprises a constant torque devicepositioned at the wheel. The constant torque device is arranged to slipat a pre-determined torque. In aspects, gearing is provided such thatthe effective winding surface diameter of the wheel is always greaterthan that required and the constant torque device slips to accommodatethis whilst maintaining desired lid sheet tension.

It will have been appreciated that the compensating means functions suchas to compensate for an increase in the diameter of the effectivewinding surface of the wheel during use of the dispenser. It will beappreciated that the initial effective winding surface and associatedinitial drive ‘speed’ of the wheel is principally a function of the(fixed) initial diameter of the wheel. Variations are envisaged hereinwhere that initial effective winding surface is selected to defineparticularly selected initial drive characteristics of the wheel.

In one variation sometimes called ‘one way take up’ mode, the initialeffective winding surface is selected such as to initially provide ideal(i.e. uniform) indexing of the medicament carrier. As lid sheet winds uparound the wheel the effective winding surface increases and thecompensating means acts such as to compensate for that increase.

In another variation sometimes called ‘two way take up’ mode, theinitial effective winding surface is selected such as to initiallyprovide non-ideal (i.e. non-uniform) indexing of the medicament carrierbecause the diameter of the lid sheet wheel is insufficiently great. Aslid sheet winds up around the wheel the effective winding surfaceincreases to an ideal diameter and then on further winding up continuesto increase to a non-ideal (i.e. too great diameter). In this embodimentit will be appreciated that the degree and nature of compensationprovided by the compensating means will vary over the winding upfunction. The compensating means initially acts such as to compensatefor the insufficient wheel diameter. That compensation then decreases tozero at the point where the diameter of the effective winding surface isideal. The compensation then progressively acts such as to compensatefor a too great effective winding surface. This approach has theadvantage of overall reducing the (average) compensating action (e.g.tension) experienced by the medicament carrier from a defined zero (i.e.the ideal) and enables the use of less powerful tensioning means (e.g.smaller springs). In a preferred aspect of this variation, the idealeffective winding surface diameter is selected to correspondapproximately to the point at which half of the lid sheet is wound up onthe wheel, in which case the average (i.e. mean) compensating actionexperienced is by the carrier over a full usage cycle is close to zero.

Alternatively, the compensating means comprises a clutch to adjust forany increase in the diameter of the effective winding surface of the liddriver during use of the dispenser. In one aspect, the clutchcommunicates with the an indexer and the lid driver, and comprises agearing surface defining plural gear engagement positions; and pluralgear teeth for engaging said plural gear engagement positions, whereinthe plural gear teeth are arranged such that at any one time only asingle gear tooth engages a single gear engagement position.

In use, the clutch acts to compensate for the increase in diameter ofsaid effective winding surface of the lid driver. The clutch allows forslippage when the tension in the lid sheet is greater than the forcerequired to peel apart the lid sheet and the base sheet.

It will be appreciated that in total, the clutch effectively defines anumber of individual gear positions that is greater than the number ofgear engagement positions. This is therefore advantageous over atraditional slipping clutch arrangement comprising intermeshing gearwheels, where the effective number of individual gear positions definedis either equal to, or no more than, the number of gear engagementpositions defined by one of the gear wheels.

Suitably, the gearing surface and plural gear teeth are arranged suchthat the number of individual gear positions defined is equal to thenumber of gear engagement positions multiplied by the number of gearteeth. In one example, if the gearing surface defines 60 gear engagementpositions and there are 6 gear teeth, then up to 360 individual gearpositions are definable (e.g. 1° resolution on a rotating gear system).

Suitably, the gearing surface defines from 20 to 100, preferably from 40to 80 gear engagement positions. Suitably, the number of gear teeth isfrom 2 to 20, preferably from 3 to 10.

In one aspect, the gear engagement positions are equally spaced (e.g.equidistantly spaced) and the gear teeth are offset (e.g.non-equidistantly spaced) relative thereto. Such offset arrangementmaximises the number of effective individual gear positions that arecapable of definition. An example of this aspect is a Vernier springarrangement.

In another aspect, the gear engagement positions are also equally spaced(e.g. equidistantly spaced) and the gear teeth are located on a wobblingelement capable of wobbling the gear teeth to plural offset (e.g.non-equidistantly spaced) positions. Such a wobbling offset arrangementalso maximises the number of effective individual gear positions thatare capable of being defined. An example of this aspect is the wobblingwheel arrangement.

In aspects, the clutch is non-integral with either of the lid driver orthe indexer, but forms a separate interconnecting component.

Suitably, the gearing surface comprises a gear wheel. As used herein,the term gear wheel encompasses, for example, a wheel, spindle or spool.Suitably, the gear teeth may be arranged to be in ratchet form (i.e.enabling movement in one direction only). Suitably, the gearing surfaceand gear teeth are in biased (e.g. sprung) engagement.

In another aspect, the lid driver comprises a mangle. The lid sheetpasses through two rotating wheels that act as a mangle and is grippedat the point of contact with the wheels. The used portion of the lidsheet is collected in a chamber after it has passed through the mangle.

In another aspect, the lid driver comprises a roller. Suitably saidroller is composed of a polymeric rubber and is positioned next to aguide wall. Suitably said roller has a smooth surface. Alternativelysaid roller has a knurled surface. The roller grips the lid sheet as itpasses from the point at which it is separated from the base sheetthrough the space between the roller and the guide wall and the usedportion of the lid sheet is then collected in a chamber. The roller hasthe advantage over the mangle described above in that a greater degreeof contact between the roller wheel and the lid sheet occurs—the lidsheet is squeezed through the roller and may pass around about ⅓ of theroller wheel. This provides a higher level of grip and pulling forcethan with a mangle. The force required to turn the roller is constantthroughout the use of the device and does not vary according to how muchof the lid sheet has been peeled away from the base sheet. This is incontrast to the wheel described above where the forces required to turnthe wheel may vary due to the fact that the lid sheet is wound aroundthe wheel. The lid sheet is not wound around the roller. The roller alsohas the advantage that the lid sheet does not have to be looped aroundor fixed to the roller before use of the device, therefore simplifyingassembly of the device and reducing costs.

In another aspect, the lid driver comprises a lid spool. Suitably, thelid spool comprises a toothed wheel with a central upward cylindricalprojection on which the lid sheet may be wound when it has beenseparated from the base sheet. The lid spool may have a mechanicalgearing mechanism which is driven on actuation of the dispenser; the lidsheet is pulled away from the base sheet and wound onto the lid spool,causing the rotatable indexing wheel to turn and index the base sheet byone dose. An interlock coupling, as described supra, may be moved alongthe base of the rotatable indexing wheel until it fits into the nextbase recess. The positioning of the interlock coupling in this recesslimits the movement of the lid spool to the distance between two pocketson the base sheet and therefore prevents the amount of lid sheet whichis wound around the lid spool from increasing as the diameter of the lidspool is increased.

In another aspect, the lid driver comprises a spiked wheel. As thespiked wheel turns, the lid sheet is pulled over it and the spikesperforate parts of the lid sheet to improve the grip on the lid sheet.The lid sheet then passes out into a chamber where it collects.

In another aspect, the lid driver comprises a clamp system. The clampsystem comprises at least one angled spring that is pivotable at one endand grips the lid sheet at the other end. The clamp system is moved inthe direction that the lid sheet is to be pulled and grips the lidsheet, pulling it and therefore peeling it away from the base sheet. Theclamp system is then moved back to its rest position. This results inthe spring pivoting and clamping the lid sheet, therefore preventing thelid sheet from being further peeled from the base sheet.

In another aspect, the used portion of the lid sheet may be passedaround rollers and fed back onto the used portion of the base sheetafter the medicament has been accessed to join back onto the base sheet.The lid sheet may be coated with a sticky substance to aid resealing.The use of this mechanism saves space, as the used portions of theblister strip will be collected in the same area.

In another aspect, the unopened medicament carrier (e.g. coiled blisterstrip) may be surrounded by a constant force spring. Alternatively, theunused blister strip may be surrounded by an elastomeric band or bandcomprising a contractible material. The constant force spring,elastomeric band or band comprising a contractible material contracts asthe coil reduces in size.

Suitably, the dispenser comprises a guide for guiding the lid sheet andbase sheet along separate paths at the opening station. The lid sheet ispassed around the guide portion onto the lid driver. In one aspect, theguide comprises a roller mechanism. The lid sheet is fed over therollers onto the lid driver.

The mechanism includes an indexer for individually indexing the distinctpockets of each of the plural medicament carriers. Suitably, the anindexer comprises a rotatable index wheel having recesses therein, saidindex wheel being engageable with a medicament carrier in use with saidmedicament dispenser such that said recesses each receive a respectivepocket of the base sheet of a blister strip in use with said medicamentdispenser.

Suitably, the rotatable index wheel additionally comprises a series ofindentations located at its base and spaced in between the recesses.

Suitably, the indexer additionally comprises an interlock coupling tocouple actuation of the dispenser to the index wheel. The interlockcoupling reversibly locks the index wheel in place. Preferably, saidinterlock coupling comprises a foot portion having a toe and a heel, anda tail section. Preferably, said interlock coupling is pivotallymountable to the dispenser at its foot portion. Preferably, said toefits into one of the indentations on the rotatable index wheel.Preferably, the interlock coupling is sprung to bias it towards locationof the toe in one of the indentations.

Alternatively, the indexer comprises a gear and sprocket wherein teethon the wheel fit into apertures or holes formed on one or both edges ofa medicament carrier. The mechanism therefore resembles that ofphotographic film being advanced through a camera.

Alternatively, the indexer comprises an index ratchet that is moveablebetween a locked position whereby said ratchet engages a pocket on saidmedicament carrier and prevents further peeling thereof, and a releaseposition allowing free movement of said medicament carrier. In thisembodiment, actuation of said medicament dispenser actuates said liddriver and releases said index ratchet from a medicament carrier toallow peeling thereof.

Suitably, the dispenser additionally comprises a first chamber in whichat least one medicament carrier is initially housed and from which it isdispensed and a second chamber to receive the used portion of the basesheet after it has been indexed around the index wheel and separatedfrom the lid sheet. Suitably, said first chamber and said second chamberare separable by a wall. In one aspect, said wall is movable to adjustthe size of said first and second chambers. In another aspect, the wallis pivotally mountable. Alternatively the wall is slidably mountable.

Suitably, the internal mechanism further comprises a third chamber toreceive the used portion of the lid sheet and a fourth chamber thathouses the index ratchet. The fourth chamber may communicate via a slit,which in turn extends upwardly within a mouthpiece and communicates withair inlets.

Suitably, the dispenser additionally comprises a crushing wheel to crushthe base sheet after the medicament has been removed from the pocketsthereof. The crushing wheel therefore reduces the space that the usedportion of the base sheet takes up.

The Applicant has now appreciated that it is advantageous if thedispensing mechanism is arranged such that it requires as little spaceas possible within the medicament dispenser, whilst not compromising itsfunction.

In one aspect, space may be saved by reducing the size of the individualcomponents of the dispensing mechanism or by arranging the components ina space efficient manner or by reducing the number of components, forexample by employing a single component to perform multiple functions.

The Applicant has found that components that may be conveniently reducedin size include the lid driver (e.g. in torsion hub or collapsible wheelform) and the indexer (e.g. in index wheel form).

The Applicants have also found that rearrangement of the relativepositioning of various components can be particularly beneficial.

In particular for space saving, it is has been found to be beneficial toposition the lid driver (e.g. torsion hub) and peel surface (e.g. beak)of the peeler in close proximity (e.g. adjacent) to each other. Such anarrangement can also enhance the effectiveness of the peeling action ofthe peeler, particularly when combined with the other ‘forcemodification’ improvements described herein below.

For space saving, it has also been found to be beneficial to positionthe common opening station and air channelling means (e.g. in the formof a manifold) to the outlet quite deeply within the device (i.e. closerto a centrally located position than to an edge located position).Adopting this configuration enables the other component parts of thedispensing mechanism and carrier (e.g. see below) to be more efficientlylocated relative to each other.

The Applicants have also appreciated that a significant amount of spacewithin the dispenser device is taken up by the plural medicamentcarriers (e.g. in elongate blister strip form). Overall space efficiencymay therefore be improved by suitable configuration of the dispensingdevice to more effectively accommodate the medicament carriers. Inparticular, where the medicament carriers are in elongate blister stripform space efficiency may be improved by reconfiguration of thedispenser to in use, most effectively contain the unpeeled strips (i.e.lid and base sheets conjoined) and peelably separated and ‘emptied ofmedicament’ parts (i.e. ‘waste’ lid and base sheets).

In one space saving improvement it has been found to be advantageous toprovide a means for tightly winding up either or both of the ‘waste’ lidsheet and base sheet of each medicament carrier. The ‘waste’ lid sheettypically winds up on the lid driver (e.g. torsion hub or collapsiblewheel form). A rotatable waste spindle may additionally be provided toreceive and tightly wind up each ‘waste’ base sheet. The waste spindlemay be common for all medicament carriers or more typically, individualwaste spindles are provided to receive ‘waste’ base sheet associatedwith each medicament carrier. Rotation of the medicament carrier istypically coupled to that of the indexer or peeler (or any drivertherefor, including a movable cover provided to the dispenser device) toensure an effective, suitably coupled winding up action.

In aspects, the movement of the ‘waste’ lid and/or base sheet take upmeans may be coupled to that of other component parts of the dispensingmechanism. In one aspect, the movement of the ‘waste’ lid and/or basesheet is arranged to be driven by the opening and/or closing of arotatable cover provided to a housing of the medicament dispenser. Inanother aspect, the movement of the ‘waste’ lid and/or base sheet takeup means is arranged to drive a mechanical counter wheel having dosecount indicia provided on the periphery thereof.

In another space saving improvement the Applicant has appreciated thatit is advantageous if each ‘waste’ base sheet is arranged for coiling upwithin a spiral track typically provided at the periphery of thedispenser device. Particular space savings are possible if for receiptof plural waste ‘base sheets’ the spiral tracks are arranged one insidethe other (i.e. co-located in a spiral sense).

In a further space saving improvement the Applicant has appreciated thatit is advantageous if both unpeeled strip and ‘waste’ base sheet areaccommodated with a common (i.e. shared) chamber. Use of such a commonchamber can however, potentially give rise to contamination problems ifthe inner cavity of the dispenser device housing that acts to house thedispensing mechanism, is not sealed off from the outside environment.Problems can particularly arise if there is the possibility ofcommunication (e.g. air/powder flow) between the common chamber and theair channelling means, which channels powder from an opened pocket atthe common opening station from the outlet for inhalation by a patient.

In one aspect, a medicament dispenser device is therefore providedherein, in which the common chamber (and parts of dispensing mechanismnecessarily housed therein) are sealed off from the outside environment,and in which the air channelling means which leads to the outlet mayonly communicate with a defined number (usually, one) of opened pocketsof each elongate form medicament carrier. Suitably, the air channellingmeans is in the form of a manifold, which includes an air inlet that inuse, allows air to be drawn into the manifold and thence, into theopened pockets to aerosolise the powder for delivery to the inhalingpatient. The form of the manifold may also be arranged to promote mixingof powder aerosolised from the opened pockets of each of the pluralmedicament carriers.

Thus, a suitable form of the manifold comprises a body defining an airchannelling means, said body provided with an inlet for enabling ingressof air to said air channelling means; a docking port for docking withone or more opened pockets of one or more medicament powder carriersherein; and an outlet for enabling egress of aerosolised pockets fromsaid one or more pockets. Mixing of powder may be encouraged by theshaping of the air channelling means and/or by the provision of featuresthereto (e.g. swirl promoting features) that encourage mixing.

In variations, the common chamber is partly or wholly sub-divided into afirst chamber and second chamber by a curtain wall that is movable toadjust the relative size of said first and second chambers. The wall mayin aspects, be pivotally mountable or slidably mountable. In analternative, the curtain wall is replaced by a bag, which expands as itbecomes filled (e.g. with ‘waste’ base sheet).

In another space saving aspect, the Applicant has found that it can beadvantageous if one or more of the elongate form medicament carriers arein the form of a peelable strip and at least, the base sheet thereof isformed as a continuous loop. In variations, the lid sheet, which forms apeelable sealing lid to the base sheet, may either have continuous loopor non-continuous loop form.

Various forms of ‘continuous loop’ type embodiment are envisagedincluding those in which the continuous loops are arranged in opposingC-loop configuration; in opposing S-loop configuration; and in flattenedloop type configurations. It will be appreciated that the form that theone or more loops defines within the dispenser device will be dictatedby space efficiency within a defined housing shape in addition todispensing functionality.

In one arrangement herein, first and second medicament-containingblister strips having base sheets in continuous loop form are positionedin ‘caterpillar track arrangement’ about respective multi-pocket indexwheels and free-running rollers. The two index wheels are arranged torotate in mutually opposing directions (i.e. one clockwise, the otheranti-clockwise) such that within the dispenser the two loops travel in amutually opposing rotary sense. In a particular aspect, the leading endof the lid foil of each strip joins to the base sheet of the otherstrip. The effect of this joining is that as each strip is rotated aboutits index wheel it results in the lid foil of the other strip beingpulled away from its base sheet (e.g. over a peel surface to peelablyseparate the lid foil from the base sheet of that other strip and openthe leading pocket thereof). In a further particular aspect, themechanism may be arranged such that as the strip is further rotatedabout its index (e.g. as a result of subsequent pocket-openingoperations) the detached (i.e. ‘waste’) lid foil thereof tends toassociate (e.g. cling to) the base sheet of the other strip to which itsend is joined. It will be appreciated that this arrangement negates theneed for any particular ‘waste’ lid foil collecting area or componentpart to be provided to the dispenser, thereby saving space.

As previously described, the dispensing mechanism suitably comprises apeeler that includes a lid driver (e.g. a torsion hub) for providingpulling force to a lid sheet and a peel surface (e.g. a beak) aboutwhich the lid sheet is pulled. These features in combination act such asto peel apart a lid sheet and a base sheet of a pocket (e.g. on receiptat the opening station) of each elongate form medicament carrier.

The Applicant has appreciated that to reduce the force required toachieve the peeling action it is desirable that as much of the pullingforce applied by the lid driver is translated into the peeling forcenecessary to peelably separate the lid sheet and base sheet. Inparticular, it is desirable that frictional losses are minimised.

Reduction of frictional losses may be achieved by making the pathbetween and peel surface and lid driver as direct and non-tortuous (e.g.non-obstructed) as possible. In particular, it is desirable that thewrap angle (i.e. that angle defined between the direction of travel ofthe lid sheet when it leaves the peel surface and the direction oftravel of the lid sheet at its point of take up by the lid driver) isminimised.

Reduction of frictional losses may also be achieved by selectingappropriate low friction materials (e.g. nylon or PTFE) for the peelsurface and indeed the lid sheet, itself. Low friction coatings may beapplied to achieve this effect.

Alternatively, reduction of frictional losses may be achieved by using amovable (e.g. rotatable) peel surface such as a beak in roller form,which rotates as lid sheet is pulled across it.

Any or all components of the dispensing mechanism may be driven byeither an electronic or mechanical drive system or combination thereof.

Suitable mechanical drive systems typically include one or moreactuators coupled via appropriate gearing (e.g. gear trains comprisingmultiple individual gears) to the drivable parts of the dispensingmechanism (e.g. the indexer, peeler and any ‘waste’ collection spindle).The one or more actuators may have simple lever form or have other formsthat enable provision of mechanical advantage. In one aspect, thedispenser device is provided with a movable cover and movement of thiscover acts to drivably actuate one or more components of the dispensingmechanism.

Suitably electronic drive means typically comprise a motor, preferablyan electrically powered motor. The motor may provide linear or rotarydrive, but in general, rotary motors are most suitable. The motor mayfor example, comprise a DC electric motor, a piezoelectric (PZ) motor,an ultrasonic motor, a solenoid motor or a linear motor. Preferably, theelectronic drive system comprises a DC motor, a PZ motor or anultrasonic motor.

The use of ultrasonic motors is particularly preferred since they offeradvantages over conventional motors in terms of weight, size, noise,cost and torque generated. Ultrasonic motors are well known in the artand are commercially available (e.g. BMSTU Technological CooperationCentre Ltd, Moscow, Russia; Shinsei Corporation, Tokyo, Japan).

Ultrasonic motors do not use coils or magnets but comprise apiezo-electric ceramic stator that drives a coupled rotor. The statorgenerates ultrasonic vibrations, which in turn causes rotation of therotor. While regular DC motors are characterised by high speed and lowtorque, requiring reduction gearing to increase torque, ultrasonicmotors attain low speed and high torque, thus eliminating the need forreduction gearing. Furthermore, these motors are lightweight andcompact, lacking coils and magnets, and are noiseless as the ultrasonicfrequencies used are not audible to the human ear.

Suitably, the dispenser further comprises actuating means for actuatinga manual or electronic drive system. Said actuating means may take theform of a switch, push-button, or lever.

The medicament dispenser herein is typically provided with a housing tohouse the dispensing mechanism thereof and in which, the outlet isprovided to the housing (e.g. as a mouthpiece for oral use or a nozzlefor nasal use).

In one aspect, the housing is provided with a movable cover toreversibly cover the outlet. The cover is therefore movable from a firstposition in which it covers the outlet (‘stowed position’) to a secondposition in which the outlet is uncovered (‘use position’). Embodimentsare envisaged in which the movement of the cover is coupled (e.g.through suitable gearing) to move one or more parts of the dispensingmechanism such as the indexer, base sheet waste spool or dose counter.

In another aspect, housing is shaped such that it may be stood uprighton a flat surface, thereby, for example enabling its ready storage onthe bedside table of a patient. In one aspect, a base is provided to thehousing for reading standing up thereon.

In one particular aspect, the dispenser herein is configured to bereloadable. In particular, each medicament carrier is suitably providedwithin a reloadable cassette.

In particular, the dispenser herein is configured to comprise a body; aholder, shaped to fit within said body and movable relative to saidbody; and receivable by said holder, a cassette containing pluralelongate form medicament carriers.

Suitably, any drive system (e.g. electronic) is located in either thebody or the holder part, and the cassette comprises the minimum numberof component (i.e. internal mechanism) parts. In embodiments, thebody/holder including the (e.g. electronic) drive is retainable by theuser and the cassette is sold as a refill/reload component that isdiscarded after use. By locating an electronic drive system in thebody/holder, the amount of electronic components that are discarded isminimised which is advantageous from an environmental standpoint.

Suitably, the cassette of the reloadable form medicament dispenserherein comprises

a) an opening station for receiving a pocket of each of the plural formmedicament carriers;

b) a peeler positioned to engage a base sheet and a lid sheet of apocket which has been received In said opening station for peeling apartsuch a base sheet and lid sheet, to open such a pocket;

c) an outlet, positioned to be in communication with an opened pocketthrough which a user can access a medicament dose portion from such anopened pocket; and

d) an indexer for individually indexing the distinct pockets of each ofthe plural medicament carriers.

Suitably, movement of the holder relative to the body results inmovement of the cassette between a first position and a second positionsuch that the cassette is reversibly removable from the holder when thecassette is in the second position.

Suitably the first position comprises a dispensing position. Preferablythe second position comprises a non-dispensing position. The cassette istherefore only removable from the holder when the cassette is in thenon-dispensing position.

Suitably, the holder and body include attaching means to attach theholder to the body. Preferably, said attaching means comprise a snap fitmechanism. Suitably said snap fit mechanism comprises a pin and holesystem.

Suitably, the holder is pivotally movable relative to the body.Alternatively the holder is rotationally movable relative to the body.

Suitably the holder additionally comprises a stop to limit movement ofthe holder relative to the body. The stop abuts against the edge of thebody at two points when it is rotated. At these points the holder may bedesigned to click into place. Therefore when the stop abuts one bodyedge then it is clicked into the dispensing position and when the stopabuts the other body edge then it is clicked into the non-dispensingposition. Alternatively the holder is slidably movable relative to thebody.

Suitably, the holder additionally comprises a catch to retain thecassette. The catch may for example comprise a sprung pin that fits intoa hole or an integral catch that deforms when pressed allowing removalof the cassette.

Suitably, the catch is child resistant. Child resistance may be realizedby having a system that forces the user to perform two actions at onceto remove the cassette. Other features of the catch may include shock orimpact resistance, the ability to lock the catch and orientationfeatures to ensure that the cassette can only be inserted one way. Thecatch should also be easy to manufacture and assemble, be robust, becomposed of a minimal number of components and intrude minimally intothe space into which the cassette is inserted.

Suitably, the holder includes guide means to guide the cassette into theholder. Preferably said guide means comprise guide rails. Alternativelythe guide means comprise grooves, indentations or other shaping orsurface details to define a ‘lock and key’ relationship between theholder and the cassette. Colour guides, arrows and any other surfacemarkings may also be employed.

Suitably, the cassette additionally comprises means to actuate thedispenser. The actuating means may take the form of a switch,push-button or lever.

Suitably, the cassette additionally comprises a mouthpiece. Suitably,said mouthpiece is extendable. The mouthpiece extends as the cassetteand holder are moved from the non-dispensing position to the dispensingposition. Alternatively the mouthpiece is retractable. The mouthpieceretracts as the cassette and holder are moved from the dispensingposition to the non-dispensing position. In one aspect, the mouthpieceis telescopic. In another aspect, the mouthpiece is fixed.

The medicament dispenser may also be designed for nasal inhalation of apowdered medicament and may therefore incorporate a nozzle as analternative to a mouthpiece. If the medicament is in solid form, thedispenser may incorporate an exit channel for tablet release.

Suitably, the body covers the mouthpiece and an indexer (and anyactuator therefor) when the cassette is in the non-dispensing position.This avoids the need for a separate cover and protects the mouthpiecefrom the ingress of dirt and contaminants during storage.

Suitably, the cassette additionally comprises a raised portion to fitagainst the holder. The raised portion is located at the opposite end ofthe cassette to the mouthpiece/nosepiece/exit and indexing lever andprevents the incorrect insertion of the cassette into the holder sinceit is too wide to fit into the holder. The raised portion is shaped suchthat it fits against a cut away part of the holder. Preferably saidraised portion includes a section that is raised to define a gripportion.

Suitably, at least a portion of the holder and body is shaped for easeof grip by the user.

The medicament dispenser in reloadable form may be supplied as a kit ofparts. A first part of the kit comprises a body; a holder, shaped to fitwithin said body and movable relative to said body; and within saidholder a receiving station for receipt of a cassette. A second part ofthe kit comprises a cassette containing plural elongate form medicamentcarriers and a dispensing mechanism for indexing said plural elongateforms medicament carriers, wherein the cassette is receivable by thereceiving station and movement of the holder relative to the bodyresults in movement of the cassette between a first position and asecond position such that the cassette is reversibly removable from thereceiving station when the cassette is in the second position. Suitably,the holder also comprises an electronic drive system for driving theindexing mechanism of the cassette.

In one aspect, the reloadable dispenser is assembled as follows. Theholder is snap fitted into the body. The cassette is assembledseparately. The body of the cassette is formed, preferably in twosections with any necessary spindles or integral components formed intothe base. Individual components such as indexing wheels, lid windingmechanisms, guide portions etc are then assembled into the base. Finallythe plural elongate form medicament carriers (e.g. blister strips) areinserted into the cassette. These may be wound into the dispenser beforethe lid is attached to the cassette and the cassette sealed.Alternatively, the cassette may be formed completely apart from a holeleft in its side for insertion of the medicament carriers. The hole maythen be sealed to complete the cassette. This second method of insertingthe medicament carriers into the device has the advantage that it ismuch simpler.

Suitably, the medicament dispenser herein comprises an actuation or dosecounter for counting the number of actuations of the indexing lever orreleases of dose from the cassette. The dose counter may count thenumber of doses left to be taken or the number of doses taken. in oneaspect, the dose counter is electronic. Alternatively said dose counteris mechanical.

In one aspect, the blister strip has printed numbers on it correspondingto the doses in the pockets. Preferably, said printed numbers arevisible through a window in the body of the dispenser or any cassettereload therefor.

Suitably, the medicament dispenser additionally comprises an electronicdata management system. The electronic data management system hasinput/output capability and comprises a memory for storage of data; amicroprocessor for performing operations on said data; and a transmitterfor transmitting a signal relating to the data or the outcome of anoperation on the data.

Suitably, the electronic data management system is arranged to beresponsive to or activated by the voice of a user. Thus, for example thesystem may be switched on or off in response to a voice command.

The electronic data management system may be integral with the body ofthe dispenser. Alternatively, the electronic data management systemforms part of a base unit that is reversibly associable with the body.

Suitably, the medicament dispenser additionally comprises a data inputsystem for user input of data to the electronic data management system.Preferably, the data input system comprises a man machine interface(MMI) preferably selected from a keypad, voice recognition interface,graphical user interface (GUI) or biometrics interface.

Energy may be conserved by a variety of means to enable the dispenser tooperate for longer on a given source of energy, such as a battery.Energy conservation or saving methods have additional advantages interms of reducing the size requirements of the power source (e.g.battery) and thus the weight and portability of the medicamentdispenser.

A variety of energy saving methods is available which generally involvereducing power consumption. One such method is to use a clock or timercircuit to switch the power on and off at regular or predeterminedintervals. In another method the system can selectively switch on/offspecific electronic devices, such as visual display units or sensors, inorder to power these devices only when they are required to perform aparticular sequence of events. Thus different electronic devices may beswitched on and off at varying intervals and for varying periods undercontrol of the system. The power sequencing system may also respond to asensor, such as a motion or breath sensor, which is activated on use ofthe device.

Low power or “micropower” components should be used within theelectronics where possible and if a high power device is required for aparticular function this should be put into a low power standby mode orswitched off when not required. Similar considerations apply in theselection of transducers. Operation at low voltage is desirable sincepower dissipation generally increases with voltage.

For low power digital applications complementary metal oxidesemi-conductor (CMOS) devices are generally preferred and these may bespecially selected by screening for low quiescent currents. Clock speedsof processors and other logic circuits should be reduced to the minimumrequired for computational throughput as power consumption increaseswith frequency. Supply voltages should also be kept at minimal valuesconsistent with reliable operation because power dissipation in charginginternal capacitance's during switching is proportional to the square ofthe voltage. Where possible, supply voltages should be approximately thesame throughout the circuit to prevent current flowing through inputprotection circuits. Logic inputs should not be left floating andcircuits should be arranged so that power consumption is minimised inthe most usual logic output state. Slow logic transitions areundesirable because they can result in relatively large class-A currentsflowing. Resistors may be incorporated in the power supply to individualdevices in order to minimise current in the event of failure.

In some control applications, devices that switch between on and offstates are preferred to those that allow analog (e.g. linear) controlbecause less power is dissipated in low resistance on states and lowcurrent off states. Where linear components are used (e.g. certain typesof voltage regulators) then types with low quiescent currents should beselected. In some circuit configurations it is preferable to useappropriate reactive components (i.e. inductors and capacitors) toreduce power dissipation in resistive components.

Suitably, the system additionally comprises a visual display unit fordisplay of data from the electronic data management system to the user.The display may for example, comprise a screen such as an LED or LCDscreen. More preferably the visual display unit is associable with thebody of the medicament dispenser.

Suitably, the medicament dispenser additionally comprises a datalink forlinking to a local data store to enable communication of data betweenthe local data store and the electronic data management system. Thedatastore may also comprise data management, data analysis and datacommunication capability.

The datastore may itself form part of a portable device (e.g. a handhelddevice) or it may be sized and shaped to be accommodated within thepatient's home. The datastore may also comprise a physical storage areafor storage of replacement cassettes. The datastore may further comprisea system for refilling medicament from a reservoir of medicament productstored therewithin. The datastore may further comprise an electricalrecharging system for recharging any electrical energy store on themedicament dispenser, particularly a battery recharging system.

The datalink may for example enable linking with a docking station, apersonal computer, a network computer system or a set-top box by anysuitable method including a hard-wired link, an infrared link or anyother suitable wireless communications link.

Suitably, the medicament dispenser additionally comprises an actuationdetector for detecting actuation of the dispensing mechanism whereinsaid actuation detector transmits actuation data to the electronic datamanagement system.

The medicament dispenser may additionally comprise a safety mechanism toprevent unintended multiple actuations of the dispensing mechanism. Thepatient is thereby protected from inadvertently receiving multiple dosesof medicament in a situation where they take a number of short rapidbreaths. More preferably, the safety mechanism imposes a time delaybetween successive actuations of the release. The time delay istypically of the order of from three to thirty seconds.

Suitably, the medicament dispenser additionally comprises a releasedetector for detecting release of medicament from the cassette, whereinsaid release detector transmits release data to the electronic datamanagement system.

Suitably, the medicament dispenser additionally comprises a shakedetector for detecting shaking of the medicament container (e.g. priorto actuation of the dispensing mechanism), wherein said shake detectortransmits shake data to the electronic data management system.

Suitably, any actuation detector, release detector, or shake detectorcomprises a sensor for detecting any suitable parameter such asmovement. Any suitable sensors are envisaged including the use ofoptical sensors. The release detector may sense any parameter affectedby release of the medicament such as pressure, temperature, sound,moisture, carbon dioxide concentration and oxygen concentration.

Suitably, the medicament dispenser additionally comprises a breathtrigger for triggering the dispensing mechanism, said breath triggerbeing actuable in response to a trigger signal from the electronic datamanagement system. Preferably, the electronic data management systemincludes a predictive algorithm or look-up table for deriving from thebreath data when to transmit the trigger signal. For example, areal-time analysis of the patient breath waveform may be made and thetrigger point derived by reference to that analyzed waveform.

Suitably, the electronic data management system includes a predictivealgorithm or look-up table for calculating the optimum amount ofmedicament to dispense.

Suitably, the memory on the electronic data management system includes adose memory for storing dosage data and reference is made to the dosememory in calculating the optimum amount of medicament to dispense.

Suitably, the medicament dispenser additionally comprises a selector forselecting the amount of medicament to dispense from said dispensingmechanism. In one aspect, the selector is manually operable. In anotheraspect, the selector is operable in response to a signal from thetransmitter on the electronic data management system.

Suitably, the medicament dispenser comprises in association with a bodyor housing thereof, a first transceiver for transmitting and receivingdata and in association with the medicament container, a secondtransceiver for transmitting and receiving data, wherein data istransferable in two-way fashion from the first transceiver to the secondtransceiver. The data is preferably in digital form and suitable fortransfer by electronic or optical means.

One advantage of embodiments of this type is the ability to store manytypes of information in different parts of the memory structure of thetransceivers. The information is furthermore stored in a form that isreadily and accurately transferable. The information could for example,include manufacturing and distribution compliance information written tothe memory at various points in the manufacturing or distributionprocess, thereby providing a detailed and readily accessible producthistory of the dispenser. Such product history information may, forexample, be referred to in the event of a product recall. The complianceinformation could, for example, include date and time stamps. Theinformation could also include a unique serial number stored inencrypted form or in a password protectable part of the memory thatuniquely identifies the product and therefore may assist in thedetection and prevention of counterfeiting. The information could alsoinclude basic product information such as the nature of the medicamentand dosing information, customer information such as the name of theintended customer, and distribution information such as the intendedproduct destination.

On loading or reloading the medicament dispenser with a cassette thesecond transceiver may, for example, read the unique serial number,batch code and expiry date of the medicament and any other informationon the second transceiver. In this way the nature and concentration ofthe medicament, together with the number of doses used or remainingwithin the cassette, may be determined. This information can bedisplayed to the patient on a visual display unit. Other information,such as the number of times the medicament dispenser has been reloadedwith a cassette, may also be displayed.

Similarly, should the cassette be removed from the holder before thesupply of medicament is exhausted, the same data can be read from thesecond transceiver and the number of doses remaining or used determined.Other information, such as the date and time of administration of thedrug, or environmental exposure data such as the minimum/maximumtemperatures or levels of humidity the cassette has been exposed to, mayalso be read and displayed to the user.

In the event that the supply of medicament within the container becomesexhausted, or that the shelf life of the medicament has expired, or thatthe first transceiver does not recognize the batch code on the secondtransceiver, activation of the dispenser may be prevented to safeguardthe user. Activation may also be prevented if the medicament has beenexposed to extreme environmental conditions for periods outwith themanufacturer's guidelines.

Data may be transferred to and from any transceiver during the period ofuse of the medicament dispenser by the patient. For example, themedicament dispenser may include an electronic data management systemhaving various sensors associated therewith. Any data collected by thesensors or from any data collection system associated with theelectronic data management system including a clock or other date/timerecorder is transferable.

Data may be transferred each time the patient uses the dispenser. Oralternatively, data may be stored in a database memory of the electronicdata management system and periodically downloaded to any transceiver.In either case, a history of the usage of the dispenser may be built upin the memory of a transceiver.

In one embodiment herein, a history of the usage of the medicamentdispenser is transferred to the second transceiver. When the medicamentcarriers in the cassette are exhausted, the cassette is exchangeable bythe patient for a new refill cassette. At the point of exchange, whichwill typically occur at the pharmacy, data may be transferred from theexhausted cassette to the refill and vice-versa. Additionally, usagehistory data may be read from the refill and transferred to a healthcaredata management system for example comprising a network computer systemunder the control of a healthcare data manager.

Methods are envisaged herein whereby the patient is given some sort ofreward for returning the refill and making available the data comprisedwithin the second transceiver. Methods are also envisaged herein wherebythe healthcare data manager is charged for either receipt of the datafrom the second transceiver or for its use for commercial purposes. Anyrewards or charging may be arranged electronically. The methods may beenabled by distributed or web-based computer network systems in whichany collected data is accessible through a hub on the network. The hubmay incorporate various security features to ensure patientconfidentiality and to allow selective access to information collecteddependent upon level of authorisation. The level of user authorisationmay be allocated primarily to safeguard patient confidentiality. Beyondthis the level of user authorisation may also be allocated on commercialterms with for example broader access to the database being authorisedin return for larger commercial payments.

Suitably, the first and second transceiver each comprise an antenna orequivalent for transmitting or receiving data and connecting thereto amemory. The memory will typically comprise an integrated circuit chip.Either transceiver may be configured to have a memory structure thatallows for large amounts of information to be stored thereon. The memorystructure can be arranged such that parts of the memory are read-only,being programmed during/after manufacture, other parts are read/writeand further parts are password protectable. Initial transfer ofinformation (e.g. on manufacture or one dispensing) to or from anytransceiver can be arranged to be readily achievable by the use of areader which is remote from the medicament dispenser, thereby minimisingthe need for direct product handling. In further aspects, the reader canbe arranged to simultaneously read or write to the memory of multipletransceivers on multiple medicament dispensers.

A suitable power source such as a battery, clockwork energy store, solarcell, fuel cell or kinetics-driven cell will be provided as required toany electronic component herein. The power source may be arranged to berechargeable or reloadable.

Suitably, data is transferable in two-way fashion between the first andsecond transceiver without the need for direct physical contacttherebetween. Preferably, data is transferable wirelessly between thefirst and second transceiver.

Suitably, the first transceiver is an active transceiver and the secondtransceiver is a passive transceiver. The term active is used to meandirectly powered and the term passive is used to mean indirectlypowered.

Suitably, the second transceiver comprises a label or tag comprising anantenna for transmitting or receiving energy; and an integrated circuitchip connecting with said antenna, and the first transceiver comprises areader for said label or tag. In this case the label or tag is a passivetransceiver and the reader is an active transceiver. Preferably, thereader will not need to be in direct contact with the tag or label toenable the tag or label to be read.

The tag may be used in combination and/or integrated with othertraditional product labeling methods including visual text,machine-readable text, bar codes and dot codes.

Suitably, the integrated circuit chip has a read only memory area, awrite only memory area, a read/write memory area or combinationsthereof.

Suitably, the integrated circuit chip has a one-time programmable memoryarea. More preferably, the one-time programmable memory area contains aunique serial number.

Suitably, the integrated circuit chip has a preset memory areacontaining a factory preset, non-changeable, unique data item. Thepreset memory item is most preferably in encrypted form.

Suitably, the integrated circuit chip has plural memory areas thereon.Suitably, any memory area is password protected.

Suitably, any memory area contains data in encrypted form. Electronicmethods of checking identity, error detection and data transfer may alsobe employed.

In one aspect, the integrated circuit has plural memory areas thereonincluding a read only memory area containing a unique serial number,which may for example be embedded at the time of manufacture; aread/write memory area which can be made read only once information hasbeen written thereto; and a password protected memory area containingdata in encrypted form which data may be of anti-counterfeiting utility.

Suitably, the tag is on a carrier and the carrier is mountable on thebody or holder of the medicament dispenser or on the cassette.

In one aspect, the carrier is a flexible label. In another aspect, thecarrier is a rigid disc. In a further aspect, the carrier is arectangular block. In a further aspect, the carrier is a collar ringsuitable for mounting to the neck of an aerosol container. Other shapesof carrier are also envisaged.

Suitably, the carrier is moldable or wieldable to the cassette orhousing. Suitably, the carrier encases the tag. More preferably, thecarrier forms a hermetic seal for the tag. In one aspect, the carriercomprises an insulating material such as a glass material or, a papermaterial or an organic polymeric material such as polypropylene.Alternatively, the carrier comprises a ferrite material.

The energy may be in any suitable form including ultrasonic, infrared,radiofrequency, magnetic, optical and laser form. Any suitable channelsmay be used to channel the energy including fibre optic channels.

In one aspect, the second transceiver comprises a radiofrequencyidentifier comprising an antenna for transmitting or receivingradiofrequency energy; and an integrated circuit chip connecting withsaid antenna, and the first transceiver comprises a reader for saidradiofrequency identifier. In this case the radiofrequency identifier isa passive transceiver and the reader is an active transceiver. Anadvantage of radiofrequency identifier technology is that the readerneed not be in direct contact with the radiofrequency identifier tag orlabel to be read.

The radiofrequency identifier can be any known radiofrequencyidentifier. Such identifiers are sometimes known as radiofrequencytransponders or radiofrequency identification (RFID) tags or labels.Suitable radiofrequency identifiers include those sold by PhillipsSemiconductors of the Netherlands under the trade marks Hitag and Icode,those sold by Amtech Systems Corporation of the United States of Americaunder the trade mark Intellitag, and those sold by Texas instruments ofthe United States of America under the trade mark Tagit. Suitably, theantenna of the RFID tag is capable of transmitting or receivingradiofrequency energy having a frequency of from 100 kHz to 2.5 GHz.Preferred operating frequencies are selected from 125 kHz, 13.56 MHz and2.4 GHz.

In one aspect, the second transceiver comprises a magnetic label or tagcomprising an antenna for transmitting or receiving magnetic fieldenergy; and an integrated circuit chip connecting with said antenna, andthe first transceiver comprises a reader for said magnetic label or tag.In this case the magnetic label or tag is a passive transceiver and thereader is an active transceiver.

A suitable magnetic label or tag comprises plural magnetic elements inmutual association whereby the magnetic elements move relative to eachother in response to an interrogating magnetic field. A magnetic labelor tag of this type is described in U.S. Pat. No. 4,940,966. Anothersuitable magnetic label or tag comprises a magnetorestrictive elementwhich is readable by application of an interrogating alternatingmagnetic field in the presence of a magnetic bias field which results inresonance of the magnetorestrictive elements at different predeterminedfrequencies. A magnetic label of this type is described in PCT PatentApplication No. WO92/12402. Another suitable magnetic label or tagcomprising plural discrete magnetically active regions in a linear arrayis described in PCT Patent Application No. WO96/31790. Suitable magneticlabels and tags include those making use of Programmable MagneticResonance (PMR) (trade name) technology.

In another aspect, the second transceiver comprises a microelectronicmemory chip and the first transceiver comprises a reader for saidmicroelectronic memory chip. The microelectronic memory chip maycomprise an Electrically Erasable Programmable Read Only Memory (EEPROM)chip or a SIM card-type memory chip. In this case the microelectronicmemory chip is a passive transceiver and the reader is an activetransceiver.

Any transceiver herein, particularly a passive transceiver may bemounted on or encased within any suitable inert carrier. The carrier maycomprise a flexible sheet that may in embodiments be capable ofreceiving printed text thereon.

In one aspect, the first transceiver is integral with the body such thata single unit is comprised. The first transceiver may for example beencased within or molded to the body.

In another aspect, the first transceiver forms part of a base unit thatis reversibly associable with the body. The base unit may for example,form a module receivable by the body such as a snap-in module.

Suitably, the medicament dispenser additionally comprises a communicatorfor wireless communication with a network computer system to enabletransfer of data between the network computer system and the electronicdata management system. Dispensers employing such communicators aredescribed in pending PCT Applications No.s PCT/EP00/09291 (PG3786),PCT/EP00/09293 (PG4029) and PCT/EP00/09292 (PG4159). Preferably, thecommunicator enables two-way transfer of data between the networkcomputer system and the electronic data management system.

Suitably, the data is communicable between the network computer systemand the electronic data management system in encrypted form. Allsuitable methods of encryption or partial encryption are envisaged.Password protection may also be employed. Suitably, the communicatoremploys radiofrequency or optical signals.

In one aspect, the communicator communicates via a gateway to thenetwork computer system. In another aspect, the communicator includes anetwork server (e.g. a web server) such that it may directly communicatewith the network.

In a further aspect, the communicator communicates with the gateway viaa second communications device. Preferably, the second communicationsdevice is a telecommunications device, more preferably a cellular phoneor pager. Preferably, the communicator communicates with the secondcommunications device using spread spectrum radiofrequency signals. Asuitable spread spectrum protocol is the Bluetooth (trade mark) standardthat employs rapid (e.g. 1600 times a second) hopping between pluralfrequencies (e.g. 79 different frequencies). The protocol may furtheremploy multiple sending of data bits (e.g. sending in triplicate) toreduce interference.

In one aspect, the network computer system comprises a public accessnetwork computer system. The Internet is one suitable example of apublic access network computer system, wherein the point of accessthereto can be any suitable entrypoint including an entrypoint managedby an Internet service provider. The public access network computersystem may also form part of a telecommunications system, which mayitself be a traditional copper wire system, a cellular system or anoptical network.

In another aspect, the network computer system comprises a privateaccess network computer system. The private access network system mayfor example, comprise an Intranet or Extranet that may for example, bemaintained by a health service provider or medicament manufacturer. Thenetwork may for example include password protection; a firewall; andsuitable encryption means.

Preferably, the communicator enables communication with a user-specificnetwork address in the network computer system.

The user-specific network address may be selected from the groupconsisting of a web-site address, an e-mail address and a file transferprotocol address. Preferably, the user-specific network address isaccessible to a remote information source such that information fromsaid remote information source can be made available thereto.

More preferably, information from the user-specific network address canbe made available to the remote information source.

In one aspect, the remote information source is a medicament prescriber,for example a doctor's practice. Information transferred from themedicament prescriber may thus, comprise changes to prescriptiondetails, automatic prescription updates or training information.Information transferred to the medicament prescriber may comprisecompliance information, that is to say information relating to thepatient's compliance with a set-prescribing programme. Patientperformance information relating for example, to patient-collecteddiagnostic data may also be transferred to the medicament prescriber.Where the dispenser is an inhaler for dispensing medicament for therelief of respiratory disorders examples of such diagnostic data wouldinclude breath cycle data or peak flow data.

In another aspect, the remote information source is a pharmacy.Information transferred from the pharmacy may thus, comprise informationrelating to the medicament product. Information sent to the pharmacy maythus include prescription requests that have been remotelypre-authorised by the medicament prescriber.

In a further aspect, the remote information source is an emergencyassistance provider, for example a hospital accident and emergencyservice or an emergency helpline or switchboard. The information maythus, comprise a distress or emergency assist signal which requestsemergency assistance.

In a further aspect, the remote information source is a manufacturer ofmedicament or medicament delivery systems. Information transferred tothe system may thus, comprise product update information. The system mayalso be configured to feed information back to the manufacturer relatingto system performance.

In a further aspect, the remote information source is a researchestablishment. In a clinical trial situation, information may thus betransferred relating to the trial protocol and information relating topatient compliance fed back to the research establishment.

In a further aspect, the remote information source is an environmentalmonitoring station. Information relating to weather, pollen counts andpollution levels may thus be made accessible to the system.

Suitably, the medicament dispenser additionally comprises a geographicpositioning system such as a global positioning system or a system thatrelies on the use of multiple communications signals and a triangulationalgorithm.

According to another aspect of the present invention, there is provideda medicament dispenser for containing plural elongate form medicamentcarriers, each having multiple distinct medicament dose portions carriedthereby, said dispenser having a housing, and within said housing adispensing mechanism for dispensing the distinct medicament doseportions carried by each of said plural medicament carriers, saidmechanism comprising,

a) at least one receiving station for receiving each of the pluralmedicament carriers;

b) a release for releasing in combination a distinct medicament doseportion from each of the plural medicament carriers on receipt thereofby said receiving station;

c) an outlet, positioned to be in communication with the distinctmedicament dose portions releasable by said release; and

d) at least one indexer for individually indexing the distinctmedicament dose portions of each of the plural medicament carriers,

wherein said dispenser further comprises a movable cover that couples tothe dispensing mechanism such that movement of said cover actuates oneor more components of the dispensing mechanism.

According to a further aspect of the present invention there is providedthe use of the dispenser herein for dispensing a combination medicamentproduct.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will now be described with reference to the accompanyingdrawings in which:

FIG. 1 shows a perspective view of a medicament carrier suitable for usein accord with the dispenser of the present invention;

FIGS. 2 and 3 show sectional plan views of medicament dispensers inaccord with the invention;

FIGS. 4 a and 4 b show sectional plan views of a medicament dispenser inaccord with one aspect of the invention respectively in ‘fully charged’with medicament and ‘fully empty’ of medicament configurations;

FIG. 5 shows a sectional plan view of a further medicament dispenser inaccord with the invention having medicament carriers with base sheets incontinuous loop form;

FIG. 6 a shows a sectional plan view of a further medicament dispenserin accord with the invention capable of receiving medicament carrierswith base sheets in continuous loop form and FIG. 6 b shows a sectionplan view of a simplified form of the medicament dispenser of FIG. 6 awith medicament carriers received thereby;

FIG. 7 a shows a sectional plan view of a further medicament dispenserin accord with the invention capable of receiving medicament carrierswith base sheets in continuous loop form and FIG. 7 b shows a sectionplan view of a simplified form of the medicament dispenser of FIG. 7 awith medicament carriers received thereby;

FIG. 8 a shows a sectional plan view of a further medicament dispenserin accord with the invention capable of receiving medicament carriers inelongate strip form and FIG. 8 b shows a section plan view of themedicament dispenser of FIG. 8 a with medicament carriers receivedthereby;

FIGS. 9 and 10 show schematic plan views of further medicamentdispensers in accord with the invention;

FIG. 11 shows schematic cutaway view of a further medicament dispenserin accord with the invention;

FIG. 12 a shows a side view of a medicament carrier arrangement suitablefor use in fold-up configuration, as shown in FIG. 12 b; and FIG. 12 cshows a medicament dispenser for receiving the carrier in fold-upconfiguration of FIG. 12 b;

FIG. 13 shows a perspective view of a lid driver suitable for use withmedicament dispensers herein;

FIGS. 14 a to 14 c show side views of a medicament dispenser herein witha movable cover drive mechanism at different stages of the cover driveaction;

FIG. 15 shows a perspective view of the inner workings of the medicamentdispenser of FIGS. 14 a to 14 c.

DETAILED DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a medicament carrier 1 suitable for use in accord with thepresent invention. The medicament carrier comprises a flexible strip 2defining a plurality of pockets 4, 6, 8 each of which contains a portionof a dose of medicament of a form suitable for inhalation and in theform of powder. In accord with the present invention, plural such strips2 are typically employed in a single medicament dispenser, wherein eachstrip provides the component medicament dose portions of a combinationmedicament product. Each strip may be of the same size and/or containthe same dose amount (e.g. volume or mass) or in alternativeembodiments, strips of different sizes and/or containing different doseamounts may be employed in combination.

The strip comprises a base sheet 10 in which blisters are formed todefine the pockets 4, 6, 8 and a lid sheet 12 which is hermeticallysealed to the base sheet except in the region of the blisters in such amanner that the lid sheet 12 and the base sheet 10 can be peeled apart.The sheets 10, 12 are sealed to one another over their whole widthexcept for the leading end portions 14, 16 where they are preferably notsealed to one another at all.

The lid 12 and base 10 sheets are each formed of a plastics/aluminiumlaminate and are suitably adhered to one another by heat sealing. Thelid sheet 12 comprises at least the following successive layers: (a)paper; adhesively bonded to (b) polyester; adhesively bonded to (c)aluminium foil; that is coated with a heat seal lacquer for bonding tothe base sheet. The base sheet 10 comprises at least the followingsuccessive layers: (a) oriented polyamide (OPA); adhesively bonded to(b) aluminium foil; adhesively bonded to (c) a third layer comprising apolymeric material (e.g. polyvinyl chloride).

The strip 2 is shown as having elongate pockets 4, 6, 8 that runtransversely with respect to the length of the strip 2. This isconvenient in that it enables a large number of pockets 4, 6, 8 to beprovided in series arrangement along a given strip 2 length. The strip 2may, for example, be provided with thirty, sixty or one hundred pocketsbut it will be understood that the strip 2 may have any suitable numberof pockets.

FIG. 2 illustrates a sectional view of the inner workings of a base unitof medicament dispenser 100 according to one aspect of the invention. Inuse, a protective cover (not shown) would be provided to the base unit100. First and second medicament-containing blister strips 101 a, 101 bare positioned within respective left and right chambers 102 a, 102 b ofthe base unit 100. Each blister strip 101 a, 101 b engages in respectivemulti-pocket index wheel 106 a, 106 b, and successive pockets arethereby guided towards a central opening station 108. Rotation of theindex wheels 106 a, 106 b is coupled together. At the opening station108, the lid foil 120 a, 120 b and base foil 121 a, 121 b parts of eachstrip 101 a, 101 b are peelably separable about beak 110 a, 110 b. Theresulting empty base foil 121 a, 121 b coils up in respective basetake-up chambers 114 a, 114 b. Rotatable base foil anchor spindle 115 a,115 b anchors the end of each respective base foil 121 a, 121 b in itschamber 114 a, 114 b. Progressive rotation of each respective anchorspindle 115 a, 115 b results in the ‘waste’ base foil 121 a, 121 b beingwound up there around into a tight coil. Typically, the rotation of eachbase spindle 115 a, 115 b is coupled to that of the respective indexwheel 106 a, 106 b. The used lid foil 120 a, 120 b feeds over itsrespective beak 110 a, 110 b and coils about common lid take-up spindle116 (which is also arranged for rotation) in the common lid take-upchamber 118.

It will be noted that common lid take-up spindle 116 comprises pluralarms 117 that splay out radially from the centre to give it an overall‘collapsible wheel’ form. In use, as lid-foil 120 a, 120 b wraps aroundthe rotating spindle 116, the arms 117 collapse inwardly therebyreducing the diameter of the spindle 116 itself but acting to maintain aroughly constant effective winding diameter as defined by the diameterof the spindle 116 in combination with the used lid foil 120 a, 120 bwrapped there around. The maintenance of this constant effective windingdiameter ensures uniform indexing of each strip 101 a, 101 b over theentire strip length.

In use, the dispenser is primed by actuating lever 126 located on theside of the dispenser to drivably rotate the index wheels 106 a, 106 band lid-take up spindle 116 to advance each blister strip 101 a, 101 b,thereby causing the leading pocket 104 a, 104 b thereof to be peeledopen. To access the contents of the opened pockets 104 a, 104 b, thepatient then breathes in through the outlet 124. This results innegative pressure being transmitted through manifold 122 to the openedleading pocket 104 a, 104 b of each strip 101 a, 101 b at the openingstation 108. This in turn, results in the medicament powder containedwithin each of the opened pockets 104 a, 104 b being drawn out throughthe common manifold 122 to the outlet 124 and hence to the patient as aninhaled combination medicament dose. It be appreciated that, mixing ofeach separately delivered component of the combined medicament producthappens as the powder is transported from each opened pocket 104 a, 104b to the outlet 124.

Importantly, the dispenser of FIG. 2 enables different medicament typesto be stored separately in each of the strips 101 a, 101 b but allowsfor the release and delivery thereof to the patient via the singleoutlet 124 as a combined inhaled product.

FIG. 3 illustrates a sectional view of the dispensing mechanism of abase unit of medicament dispenser 200 according to another aspect of theinvention. In use, a protective cover (not shown) would be provided tothe base unit 200 to provide a sealed cavity housing for parts of thedispensing mechanism of the dispenser 200 and blister strips 201 a, 201b contained there within.

First and second medicament-containing blister strips 201 a, 201 b arepositioned within respective left and right chambers 202 a, 202 b of thebase unit 200. As shown, the first medicament strip 201 a is shown inthe ‘fully empty’ of medicament (i.e. end of life) configuration and thesecond medicament strip 201 b is shown in the ‘fully charged’ withmedicament (i.e. start of life) configuration. It will be appreciated,that this is necessarily an artificial view since in use, both stripswill typically be equally full or empty (i.e. their configurationsmirror one other). This artificial view is thus, used for illustrationonly in order that the configuration of the dispensing mechanism of thedevice 200 may be understood as the strip 201 a, 201 b travels throughthe device.

Each blister strip 201 a, 201 b engages in its respective five pocketindex wheel 206 a, 206 b, and successive pockets are thereby guidedtowards a central opening station 208. The rotation of the index wheels206 a, 206 b is suitably coupled together. At the opening station 208,the lid foil 220 a, 220 b and base foil 221 a, 221 b parts of each strip201 a, 201 b are peelably separable about beak 210 a, 210 b. Theresulting empty base foil 221 a, 221 b coils up in respective basetake-up chambers 214 a, 214 b. Rotatable base foil anchor spindle 215 a,215 b anchors the end of each respective base foil 221 a, 221 b in itschamber 214 a, 214 b. Progressive rotation of each respective anchorspindle 215 a, 215 b results in ‘waste’ base foil 221 a, 221 b beingwound up there around into a tight coil. Typically, the rotation of eachbase spindle 215 a, 215 b is coupled to that of the respective indexwheel 206 a, 206 b.

Flexible arms 211 a, 211 b pivoted at pivot points 213 a, 213 b areprovided to each respective base take-up chamber 214 a, 214 b and act asa movable wall thereto. It will be seen that in the ‘fully charged’(i.e. start of life) position of the right hand side of the dispenser200 the flexible arm 211 b acts on the medicament-charged strip 201 b tocompress it into a minimum space. In the ‘fully empty’ (i.e. end oflife) position of the left hand side of the dispenser 200 the flexiblearm 211 a acts on the ‘waste’ base foil 221 a to again compress it intoa minimum space. The flexible arms 211 a, 211 b thereby act overall toreduce the space occupied by the strip 201 a, 201 b (when full or empty)in the dispenser device 200.

The used lid foil 220 a, 220 b feeds over its respective beak 210 a, 210b and coils about respective lid take-up spindles 216 a, 216 b, whichalso rotate to wind up lid foil 220 a, 220 b thereon. Each lid take-upspindle 216 a, 216 b is provided with a centrally located torsion spring217 a, 217 b. The function of the torsion spring 217 a, 217 b is toensure a roughly constant driving tension is provided to each strip 201a, 201 b by its lid take-up spindle 216 a, 216 b over the course of eachentire strip length. In particular, each torsion spring 217 a, 217 bacts to compensate for the variation in drive tension associated withthe increase in the effective winding diameter of each lid take-upspindle 216 a, 216 b as used lid foil 220 a, 220 b gradually becomeswrapped there around. Thus, uniform indexing of each strip 201 a, 201 bmay be maintained over the entire strip length.

In use, the dispenser is primed by actuating lever 226 located on theside of the dispenser to drivably rotate (e.g. by use of a suitable geararrangement) the index wheels 206 a, 206 b and lid-take up spindles 216a, 216 b to advance each blister strip 201 a, 201 b, thereby causing theleading pocket 204 a, 204 b thereof to be peeled open and brought intocommunication with manifold 222, which itself communicates withmouthpiece-form outlet 224. As previously mentioned, the inner workingsand blister strips 201 a, 201 b of the dispenser 200 are comprisedwithin a sealed housing. Only the leading pockets 204 a, 204 b of eachstrip 201 a, 201 b may therefore communicate with the manifold 222 andthence to the outside environment via the outlet 224. Air inlet 223 isprovided to the manifold 222 to assist in aerosolising medicament in theopened pockets 204 a, 204 b as described below.

To access the medicament contents of the opened pockets 204 a, 204 b,the patient breathes in through the outlet 224. This results in airbeing drawn into the manifold 222 through the air inlet 223 thereof, andthat air being through manifold 222 to the opened leading pocket 204 a,204 b of each strip 201 a, 201 b at the opening station 208. In turn,this results in the medicament powder contained within each of theopened pockets 204 a, 204 b being aerosolised and guided through thecommon manifold 222 to the outlet 224 and hence to the patient as aninhaled combination medicament dose. It be appreciated that, mixing ofeach separately delivered component of the combined medicament producthappens as the powder is transported from each opened pocket 204 a, 204b to the outlet 224. In embodiments, the manifold 222 is shaped topromote such mixing.

FIGS. 4 a and 4 b illustrate sectional views of the inner workings ofmedicament dispenser 300 according to another aspect of the invention.In use, a protective cover (not shown) would be provided to the baseunit 300 to provide a sealed cavity housing for the parts of thedispensing mechanism and blister strips 301 a, 301 b contained therewithin.

First and second medicament-containing blister strips 301 a, 301 b arepositioned within respective left and right chambers 302 a, 302 b of thebase unit 300. In FIG. 4 a, the medicament strips 301 a, 301 b are bothin the ‘fully charged’ with medicament (i.e. start of life)configuration. In FIG. 4 b, the medicament strips 301 a, 301 b are bothin the ‘fully empty’ of medicament (i.e. end of life) configuration.

Each blister strip 301 a, 301 b engages in its respective five pocketindex wheel 306 a, 306 b, and successive pockets are thereby guidedtowards a central opening station 308. The rotation of the index wheels306 a, 306 b is suitably coupled together. At the opening station 308,the lid foil 320 a, 320 b and base foil 321 a, 321 b parts of each strip301 a, 301 b are peelably separable about beak 310 a, 310 b. Theresulting empty base foil 321 a, 321 b coils up in respective basetake-up chambers 314 a, 314 b. Rotatable base foil anchor spindle 315 a,315 b anchors the end of each respective base foil 321 a, 321 b in itschamber 314 a, 314 b. Progressive rotation of each respective anchorspindle 315 a, 315 b results in ‘waste’ base foil 321 a, 321 b beingwound up there around into a tight coil. Typically, the rotation of eachbase spindle 315 a, 315 b is coupled to that of the respective indexwheel 306 a, 306 b.

The used lid foil 320 a, 320 b feeds over its respective beak 310 a, 310b and coils about respective lid take-up spindles 316 a, 316 b, whichalso rotate to wind up lid foil 320 a, 320 b thereon. Each lid take-upspindle 316 a, 316 b is provided with a centrally located torsion spring317 a, 317 b. The function of the torsion spring 317 a, 317 b is toensure a roughly constant driving tension is provided to each strip 301a, 301 b by its lid take-up spindle 316 a, 316 b over the course of eachentire strip length. In particular, each torsion spring 317 a, 317 bacts to compensate for the variation in drive tension associated withthe increase in the effective winding diameter of each lid take-upspindle 316 a, 316 b as used lid foil 320 a, 320 b gradually becomeswrapped there around. Thus, uniform indexing of each strip 301 a, 301 bmay be maintained over the entire strip length.

In use, the dispenser is primed by actuating lever 326 located on theside of the dispenser to drivably rotate the index wheels 306 a, 306 band lid-take up spindles 316 a, 316 b to advance each blister strip 301a, 301 b, thereby causing the leading pocket 304 a, 304 b thereof to bepeeled open and brought into communication with manifold 322, whichitself communicates with mouthpiece-form outlet 324. As previouslymentioned, the inner workings and blister strips 301 a, 301 b of thedispenser 300 are comprised within a sealed housing. Only the leadingpockets 304 a, 304 b of each strip 301 a, 301 b may thereforecommunicate with the manifold 322 and thence to the outside environmentvia the outlet 324. An air inlet 323 is provided to the manifold 322 toassist in aerosolising medicament in the opened pockets 304 a, 304 b asdescribed below.

To access the medicament contents of the opened pockets 304 a, 304 b,the patient breathes in through the outlet 324. This results in airbeing drawn into the manifold 322 through the air inlet 323 thereof, andthat air being through manifold 322 to the opened leading pocket 304 a,304 b of each strip 301 a, 301 b at the opening station 308. In turn,this results in the medicament powder contained within each of theopened pockets 304 a, 304 b being aerosolised and guided through thecommon manifold 322 to the outlet 324 and hence to the patient as aninhaled combination medicament dose. It be appreciated that, mixing ofeach separately delivered component of the combined medicament producthappens as the powder is transported from each opened pocket 304 a, 304b to the outlet 324. In embodiments, the manifold 322 is shaped topromote such mixing.

By making reference to both FIGS. 4 a and 4 b the amount and position ofthe space occupied by each strip 301 a, 301 b may be appreciated as thestrip 301 a, 301 b travels through the device. In general terms, in the‘fully charged’ (i.e. start of life) configuration the bulk of space isoccupied by coils of charged strip 301 a, 301 b. In the ‘fully empty’(i.e. end of life) configuration the bulk of space is occupied by coilsof empty base foil 321 a, 321 b. The locus of the ‘occupied’ space mayalso be seen to shift slightly (i.e. downwards and to the central axis,as illustrated) as the strip 301 a, 301 b travels through the device.

FIG. 5 illustrates a sectional view of base unit 400 of a medicamentdispenser according to the invention. In use, a protective cover (notshown) would be provided to the base unit 400. First and secondmedicament-containing blister strips 401 a, 401 b are positioned aboutleft and right lobes 402 a, 402 b of the base unit 400. Each blisterstrip 401 a, 401 b has a continuous loop form. That is to say, eachstrip comprises a continuous loop of base foil 421 a, 421 b havingpockets 404 a, 404 b for containing medicament arranged along themajority of its length; and a strip of lid foil 420 a, 420 b provided tothe base foil 421 a, 421 b to initially seal at least all of the pockets404 a, 404 b. Within the dispenser the strip 401 a, 401 b snakes aroundhub 405 a, 405 b and guiding wall 407 a, 407 b that generally act todefine the shape of each loop 401 a, 401 b when housed in the dispenserunit 400.

Each blister strip 401 a, 401 b engages in respective multi-pocket indexwheel 406 a, 406 b, and successive pockets are thereby guided towards acentral opening station 408. The rotation of the index wheels 406 a, 406b is optionally coupled together. At the opening station 408, the lidfoil 420 a, 420 b and base foil 421 a, 421 b parts of each strip 401 a,401 b are peelably separable about beak 410 a, 410 b. In contrast to theembodiment of FIG. 2 (for example), the resulting empty base foil 421 a,421 b is not coiled up. Rather, because it is joined (in ‘continuousloop’ fashion) to the tail end of the strip 401 a, 401 b it continues tobe transported through the dispenser as the strip 401 a, 401 b isfurther advanced. The need for any distinct base foil take-up chamber(e.g. see chambers 114 a, 114 b of FIG. 2) is thereby avoided.

The used lid foil 420 a, 420 b feeds over its respective beak 410 a, 410b and coils about respective lid take-up spindles 416 a, 416 b inrespective common lid take-up chambers 418 a, 418 b, which also rotateto wind up lid foil 420 a, 420 b thereon. Each lid take-up spindle 416a, 416 b is provided with a centrally located torsion spring 417 a, 417b. The function of the torsion spring 417 a, 417 b is to ensure aroughly constant driving tension is provided to each strip 401 a, 401 bby its lid take-up spindle 416 a, 416 b over the course of each entirestrip length. In particular, each torsion spring 417 a, 417 b acts tocompensate for the variation in drive tension associated with theincrease in the effective winding diameter of each lid take-up spindle416 a, 416 b as used lid foil 420 a, 420 b gradually becomes wrappedthere around. Thus, uniform indexing of each strip 401 a, 401 b may bemaintained over the entire strip length.

In use, the dispenser is primed by actuating lever 426 located on theside of the dispenser to drivably actuate the index wheels 406 a, 406 bto advance each blister strip 401 a, 401 b, thereby causing the leadingpocket 404 a, 404 b thereof to be peeled open. To access the contents ofthe opened pockets 404 a, 404 b, the patient then breathes in throughthe outlet 424. This results in negative pressure being transmittedthrough manifold 422 to the opened leading pocket 404 a, 404 b of eachstrip 401 a, 401 b at the opening station 408. This in turn, results inthe medicament powder contained within each of the opened pockets 404 a,404 b being drawn out through the common manifold 422 to the outlet 424and hence to the patient as an inhaled combination medicament dose. Itbe appreciated that, mixing of each separately delivered component ofthe combined medicament product happens as the powder is transportedfrom each opened pocket 404 a, 404 b to the outlet 424.

FIGS. 6 a and 6 b illustrate a sectional view of base unit 500 of amedicament dispenser according to the invention. It will be appreciatedthat the dispenser of FIGS. 6 a and 6 b is a variation of that shown inFIG. 5, but with the positioning of he component parts of the dispensingmechanism positioned slightly differently to accommodate generallyC-shaped loops of carrier strip.

In use, a protective cover (not shown) would be provided to the baseunit 500. As shown in FIG. 6 b only, first and secondmedicament-containing blister strips 501 a, 501 b are positioned aboutleft and right lobed structures 502 a, 502 b of the base unit 500. Eachblister strip 501 a, 501 b (visible in FIG. 6 b only) has a continuousloop form. That is to say, each strip comprises a continuous loop ofbase foil 521 a, 521 b having pockets 504 a, 504 b for containingmedicament arranged along the majority of its length; and a strip of lidfoil 520 a, 520 b provided to the base foil 521 a, 521 b to initiallyseal at least all of the pockets 504 a, 504 b. Within the dispenser thestrip 501 a, 501 b snakes around hub walls 505 a, 505 b and guide walls507 a, 507 b that generally act to define the shape of each loop 501 a,501 b when housed in the dispenser unit 500.

Each blister strip 501 a, 501 b engages in respective multi-pocket indexwheel 506 a, 506 b, and successive pockets are thereby guided towards acentral opening station 508. The rotation of the index wheels 506 a, 506b is optionally coupled together. At the opening station 508, the lidfoil 520 a, 520 b and base foil 521 a, 521 b parts of each strip 501 a,501 b are peelably separable about beak 510 a, 510 b. In contrast to theembodiment of FIG. 2 (for example), the resulting empty base foil 521 a,521 b is not coiled up. Rather, because it is joined (in ‘continuousloop’ fashion) to the tail end of the strip 501 a, 501 b it continues tobe transported through the dispenser as the strip 501 a, 501 b isfurther advanced. The need for any distinct base foil take-up chamber(e.g. see chambers 114 a, 114 b of FIG. 2) is thereby avoided.

The used lid foil 520 a, 520 b feeds over its respective beak 510 a, 510b and coils about respective lid take-up spindles 516 a, 516 b, whichalso rotate to wind up lid foil 520 a, 520 b thereon. Each lid take-upspindle 516 a, 516 b is provided with a centrally located torsion spring517 a, 517 b. The function of the torsion spring 517 a, 517 b is toensure a roughly constant driving tension is provided to each strip 501a, 501 b by its lid take-up spindle 516 a, 516 b over the course of eachentire strip length. In particular, each torsion spring 517 a, 517 bacts to compensate for the variation in drive tension associated withthe increase in the effective winding diameter of each lid take-upspindle 516 a, 516 b as used lid foil 520 a, 520 b gradually becomeswrapped there around. Thus, uniform indexing of each strip 501 a, 501 bmay be maintained over the entire strip length.

In use, the dispenser is primed by actuating levers 526 a, 526 b locatedon each side of the dispenser (which in embodiments could be replaced bya common lever 526) to drivably actuate the index wheels 506 a, 506 b toadvance each blister strip 501 a, 501 b, thereby causing the leadingpocket 504 a, 504 b thereof to be peeled open. To access the contents ofthe opened pockets 504 a, 504 b, the patient then breathes in throughthe outlet 524. This results in negative pressure being transmittedthrough manifold 522 to the opened leading pocket 504 a, 504 b of eachstrip 501 a, 501 b at the opening station 508. This in turn, results inthe medicament powder contained within each of the opened pockets 504 a,504 b being drawn out through the common manifold 522 to the outlet 524and hence to the patient as an inhaled combination medicament dose. Itbe appreciated that, mixing of each separately delivered component ofthe combined medicament product happens as the powder is transportedfrom each opened pocket 504 a, 504 b to the outlet 524.

FIGS. 7 a and 7 b illustrate a sectional view of base unit 600 of amedicament dispenser according to the invention. It will be appreciatedthat the dispenser of FIGS. 7 a and 7 b is a variation of that shown inFIG. 5, but with a common take-up spindle and also with the positioningof the component parts of the dispensing mechanism positioned slightlydifferently to accommodate generally S-shaped loops of carrier strip.

In use, a protective cover (not shown) would be provided to the baseunit 600. As shown in FIG. 7 b only, first and secondmedicament-containing blister strips 601 a, 601 b are positioned abouttop and bottom S-shaped structures 602 a, 602 b of the base unit 600.Each blister strip 601 a, 601 b (visible in FIG. 7 b only) has acontinuous loop form. That is to say, each strip comprises a continuousloop of base foil 621 a, 621 b having pockets 604 a, 604 b forcontaining medicament arranged along the majority of its length; and astrip of lid foil 620 a, 620 b provided to the base foil 621 a, 621 b toinitially seal at least all of the pockets 604 a, 604 b. Within thedispenser the strip 601 a, 601 b snakes around hub walls 605 a, 605 band guide walls 607 a, 607 b that generally act to define the S-shape ofeach loop 601 a, 601 b when housed in the dispenser unit 600.

Each blister strip 601 a, 601 b engages in respective multi-pocket indexwheel 606 a, 606 b, and successive pockets are thereby guided towards acentral opening station 608. The rotation of the index wheels 606 a, 606b is optionally coupled together. At the opening station 608, the lidfoil 620 a, 620 b and base foil 621 a, 621 b parts of each strip 601 a,601 b are peelably separable about beak 610 a, 610 b. In contrast to theembodiment of FIG. 2 (for example), the resulting empty base foil 621 a,621 b is not coiled up. Rather, because it is joined (in ‘continuousloop’ fashion) to the tail end of the strip 601 a, 601 b it continues tobe transported through the dispenser as the strip 601 a, 601 b isfurther advanced. The need for any distinct base foil take-up chamber(e.g. see chambers 114 a, 114 b of FIG. 2) is thereby avoided. The usedlid foil 620 a, 620 b feeds over its respective beak 610 a, 610 b andcoils about common lid take-up spindle 616, which also rotate to wind uplid foil 620 a, 620 b thereon. The lid take-up spindle 616 is providedwith a centrally located torsion spring 617. The function of the torsionspring 617 is to ensure a roughly constant driving tension is providedto each strip 601 a, 601 b by lid take-up spindle 616 over the course ofeach entire strip length. In particular, the torsion spring 617 acts tocompensate for the variation in drive tension associated with theincrease in the effective winding diameter of each lid take-up spindle616 as used lid foil 620 a, 620 b gradually becomes wrapped therearound. Thus, uniform indexing of each strip 601 a, 601 b may bemaintained over the entire strip length.

In use, the dispenser is primed by actuating levers 626 located on theside of the dispenser to drivably actuate the index wheels 606 a, 606 bto advance each blister strip 601 a, 601 b, thereby causing the leadingpocket 604 a, 604 b thereof to be peeled open. To access the contents ofthe opened pockets 604 a, 604 b, the patient then breathes in throughthe outlet 624. This results in negative pressure being transmittedthrough manifold 622 to the opened leading pocket 604 a, 604 b of eachstrip 601 a, 601 b at the opening station 608. This in turn, results inthe medicament powder contained within each of the opened pockets 604 a,604 b being drawn out through the common manifold 622 to the outlet 624and hence to the patient as an inhaled combination medicament dose. Itbe appreciated that, mixing of each separately delivered component ofthe combined medicament product happens as the powder is transportedfrom each opened pocket 604 a, 604 b to the outlet 624.

FIGS. 8 a and 8 b illustrate a sectional view of the dispensingmechanism of a base unit of medicament dispenser 700 according to oneaspect of the invention. FIG. 8 a shows the dispenser absent medicamentcarrier and FIG. 8 b shows the dispenser containing two blister stripform medicament carriers in the ‘end of life’ (i.e. all medicamentdispensed) configuration.

In use, a protective cover (not shown) would be provided to the baseunit 700. The base unit 700 is arranged such that first and secondmedicament-containing blister strips initially coil up within respectivefirst and second chambers 702 a, 702 b of the base unit 700. Eachblister strip engages in respective multi-pocket index wheel 706 a, 706b, and successive pockets are thereby guided towards a central openingstation 708. The rotation of the index wheels 706 a, 706 b is suitablycoupled together.

At the opening station 708, the lid foil 720 a, 720 b and base foil 721a, 721 b parts of each strip are peelably separable about beak 710 a,710 b. The resulting ‘Waste’ base foil 721 a, 721 b is directed towardsspiral-shaped track 705, which accommodates the ‘waste’ base foil 721 a,721 b in relative back-to-back alignment. As shown in FIG. 8 b, the‘waste’ base foils 721 a, 721 b are therefore stowed in a spiralconfiguration (whose shape is defined by the spiral track 705) thatlocates at the periphery of the dispensing mechanism.

The used lid foil 720 a, 720 b feeds over its respective beak 710 a, 710b and coils about its lid take-up spindle 716 a, 716 b (which is alsorotatable). The lid take-up spindle 716 a, 716 b generally takes theform of a torsion hub.

In use, the dispenser is primed by drivably actuating the index wheels706 a, 706 b and lid-take up spindles 716 a, 716 b to advance eachblister strip thereby causing the leading pocket thereof to be peeledopen. To access the contents of the opened pockets the patient thenbreathes in through an outlet (not visible). This results in negativepressure being transmitted through manifold (not visible) to the openedleading pocket of each strip at the opening station 708. This in turn,results in the medicament powder contained within each of the openedpockets being drawn out through the manifold to the outlet and hence tothe patient as an inhaled combination medicament dose. It be appreciatedthat, mixing of each separately delivered component of the combinedmedicament product happens as the powder is transported from each openedpocket to the outlet.

FIG. 9 illustrates a schematic view of dispensing mechanism 800 of amedicament dispenser according to the invention. In use, the mechanismwould be enclosed within a device housing defining a mouthpiece outlet.

As shown, first and second medicament-containing blister strips 801 a,801 b are positioned in ‘caterpillar track arrangement’ about respectivemulti-pocket index wheels 806 a, 806 b and free-running rollers 805 a,805 b. Each blister strip 801 a, 801 b has a continuous loop form. Thatis to say, each strip comprises a continuous loop of base foil 821 a,821 b having pockets 804 a, 804 b for containing medicament regularlyspaced there along; and a strip of lid foil 820 a, 820 b provided to thebase foil 821 a, 821 b to initially seal at least all of the pockets 804a, 804 b. The two index wheels 806 a, 806 b are arranged to rotate inmutually opposing directions (i.e. one clockwise, the otheranti-clockwise) such that within the dispenser the two strip 801 a, 801b travel in a mutually opposing rotary sense.

Each blister strip 801 a, 801 b engages in respective multi-pocket indexwheel 806 a, 806 b, and successive pockets are thereby guided towards acentral opening station 808. The rotation of the index wheels 806 a, 806b is coupled together. At the opening station 808, the lid foil 820 a,820 b and base foil 821 a, 821 b parts of each loop 801 a, 801 b arepeelably separable about beak 810 a, 810 b. The resulting empty basefoil 821 a, 821 b continues to be transported through the dispenser asthe continuous loop form strip 801 a, 801 b is further advanced. Theneed for any distinct base foil take-up chamber (e.g. see chambers 114a, 114 b of FIG. 2) is thereby avoided.

The leading end of the lid foil 820 a, 820 b of each strip 801 a, 801 bmay be seen to be joined at join point 830 a, 830 b to the base sheet821 b, 821 a of the other strip. The effect of this joining is that aseach strip 801 a, 801 b is rotated about its index wheel 806 a, 806 b itresults in the lid foil 820 b, 820 a of the other strip being pulledover its respective beak 810 b, 810 a to peelably separate the lid foil820 b, 820 a from the base sheet 821 b, 821 a of that other strip 801 b,801 a and open the leading pocket 804 b, 804 a thereof. As the strip 801a, 801 b is further rotated about its index wheel 806 a, 806 b (e.g. asa result of subsequent pocket-opening operations) the detached (i.e.‘waste’) lid foil 820 b, 820 a tends to associate (e.g. cling to) thebase sheet 821 a, 821 b of the other strip to which its end is joined.It will be appreciated that this arrangement negates the need for anyparticular ‘waste’ lid foil collecting area or component part to beprovided to the dispenser, thereby saving space.

In use therefore, the dispenser is primed by drivably actuating theindex wheels 06 a, 806 b to advance each blister strip 801 a, 801 b,thereby causing the leading pocket 804 a, 804 b thereof to be peeledopen. An appropriate ratchet mechanism is employed to ensure that ineach actuating movement, each blister strip 801 a, 801 b is only movedsufficiently to open one pocket 804 a, 804 b thereof. To access thecontents of the opened pockets 804 a, 804 b, the patient then breathesin through an outlet (not shown). This results in negative pressurebeing transmitted through manifold 822 to the opened leading pocket 804a, 804 b of each strip 801 a, 801 b at the opening station 808. This inturn, results in the medicament powder contained within each of theopened pockets 804 a, 804 b being drawn out through the common manifold822 to the outlet (not shown) and hence to the patient as an inhaledcombination medicament dose. It be appreciated that, mixing of eachseparately delivered component of the combined medicament producthappens as the powder is transported from each opened pocket 804 a, 804b to the outlet 824.

FIG. 10 illustrates a schematic view of dispensing mechanism 900 of amedicament dispenser according to the invention. In use, the mechanismwould be enclosed within a device housing defining a mouthpiece outlet.It will be appreciated from the detailed description below that themechanism is a ‘hybrid’ dispensing mechanism suitable for use with amedicament carrier in blister strip form that nestles within a secondmedicament carrier in continuous loop form.

First medicament carrier 901 a is in strip form and second medicamentcarrier is in continuous loop form 901 b, each comprising blistersspaced regularly there along. Each medicament carrier 901 a, 901 bengages in respective multi-pocket index wheel 906 a, 906 b, andsuccessive blister pockets are thereby guided towards a central openingstation 908. The rotation of the index wheels 906 a, 906 b is coupledtogether. At the opening station 908, the lid foil 920 a, 920 b and basefoil 921 a, 921 b parts of each strip 901 a, 901 b are peelablyseparable about beak 910 a, 910 b.

The resulting ‘waste’ base foil 921 a of the strip form carrier 901 acoils up in base take-up chamber 914 a. Rotatable base foil anchorspindle 915 a anchors the end of the base foil 921 a in the chamber 914a. Progressive rotation of the anchor spindle 915 a results in the‘waste’ base foil 921 a being wound up there around into a tight coil.Typically, the rotation of the base spindle 915 a is coupled to that ofits index wheel 906 a. The ‘waste’ lid foil 920 a of the strip formcarrier 901 a feeds over its respective beak 910 a and coils about itslid take-up spindle 916 a.

The resulting ‘waste’ base foil 921 b of the continuous loop formcarrier 901 b is not coiled up. Rather, because it joins (in ‘continuousloop’ fashion) to the tail end of the strip 901 b it continues to betransported through the dispenser, as the strip 901 b is furtheradvanced. The need for any distinct base foil take-up spindle is therebyavoided. The ‘waste’ lid foil 920 b of the continuous loop form carrier901 b feeds over its respective beak 910 b and coils about its lidtake-up spindle 916 b.

In use, the dispenser is primed by drivably rotating both respectiveindex wheels 906 a, 906 b and lid-take up spindles 916 a, 916 b toadvance each medicament carrier 901 a, 901 b, thereby causing theleading pocket 904 a, 904 b thereof to be peeled open. To access thecontents of the opened pockets 904 a, 904 b, the patient then breathesin through an outlet (not shown). This results in negative pressurebeing transmitted through common manifold 922 to the opened leadingpocket 904 a, 904 b of each strip 901 a, 901 b at the opening station908. This in turn, results in the medicament powder contained withineach of the opened pockets 904 a, 904 b being drawn out through thecommon manifold 922 to the outlet 924 and hence to the patient as aninhaled combination medicament dose. It be appreciated that, mixing ofeach separately delivered component of the combined medicament producthappens as the powder is transported from each opened pocket 904 a, 904b to the outlet 924.

FIG. 11 illustrates a schematic view of dispensing mechanism 1000 of amedicament dispenser according to the invention. In use, the mechanismwould be enclosed within a device housing defining a mouthpiece outlet.

First 1001 a and second 1001 b medicament-containing blister strips arepositioned in ‘caterpillar track arrangement’. As drawn, only thedetails of the first medicament-containing blister strip 1001 a arevisible, but it will be appreciated that the second strip 1001 b mirrorsits form and layout.

The first medicament-containing blister strip 1001 a is retainedcaterpillar-like by multi-pocket index wheel 1006 and free-runningroller 1005. The blister strip 1001 a has a continuous loop form. Thatis to say, it comprises a continuous loop of base to foil 1021 a havingpockets 1004 a for containing medicament regularly spaced there along;and a strip of lid foil 1020 a provided to the base foil 1021 a toinitially seal at least all of the pockets 1004 a.

The blister strip 1001 a engages in respective multi-pocket index wheel1006 and by rotation thereof successive pockets are thereby guidedtowards a central opening station 1008. At the opening station 1008, thelid foil 1020 a and base foil 1021 a parts of the loop 1001 a arepeelably separable about beak 1010. The resulting empty base foil 1021 acontinues to be transported through the dispenser as the continuous loopform strip 1001 a is further advanced. The need for any distinct basefoil take-up chamber (e.g. see chambers 114 a, 114 b of FIG. 2) isthereby avoided.

The leading end of the lid foil 1020 a of the strip 1001 a may be seento be looped back over the end roller 1005, then over opposing beak 1012and finally joined at join point 1030 a to its base sheet 1021 a of thestrip 1001 a. The effect of this ‘doubling-back’ of the lid foil 1020 aand joining to the base sheet 1021 a as shown, is that as the strip 1001a is rotated about its index wheel 1006 a the leading end of lid foil1020 a is pulled further over opposing beak 1012, transmitting pullingforce through the lid foil 1020 a via end roller 1005 and then beak 1010to peelably separate the lid foil 1020 a from the base sheet 1021 a ofthe strip 1001 a, and open the leading pocket 1004 a thereof. As thestrip 1001 a is further rotated about its index wheel 1006 a (e.g. as aresult of subsequent pocket-opening operations) the detached (i.e.‘waste’) lid foil 1020 a tends to be retained in looped position aroundthe end roller 1005 and opposing beak 1012 and ultimately pulled towardsthe ‘waste’ base sheet 1021 a to which its end is joined. It will beappreciated that this arrangement negates the need for any particular‘waste’ lid foil collecting area or component part to be provided to thedispenser, thereby saving space.

In use therefore, the dispenser is primed by drivably actuating theindex wheels 1006 a to advance each blister strip 1001 a thereby causingthe leading pocket 1004 a thereof to be peeled open. An appropriateratchet mechanism is employed to ensure that in each actuating movement,each blister strip 1001 a is only moved sufficiently to open one pocket1004 a thereof. To access the contents of the opened pockets 1004 a thepatient then breathes in through an outlet (not shown). This results innegative pressure being transmitted through manifold (not shown) to theopened leading pocket 1004 a of each strip 1001 a at the opening station1008. This in turn, results in the medicament powder contained withineach of the opened pockets 1004 a being drawn out through the commonmanifold to the outlet (not shown) and hence to the patient as aninhaled combination medicament dose. It be appreciated that, mixing ofeach separately delivered component of the combined medicament producthappens as the powder is transported from each opened pocket 1004 a tothe outlet.

FIG. 12 a shows a side view of a continuous loop form medicament carrier1101 a, 1101 b arrangement suitable for use in fold-up configuration, asshown in FIG. 12 b. FIG. 12 c shows a medicament dispenser 1100 forreceiving the foldable carrier configuration of FIG. 12 b.

Referring now to FIGS. 12 a and 12 b, first and secondmedicament-containing blister strips 1101 a, 1101 b are retained inside-by-side ‘caterpillar track arrangement’ by end-located, commonmulti-pocket index wheels 1105, 1106 (e.g. 6 mm index wheels). Eachblister strip 1101 a, 1101 b has a continuous loop form. That is to say,each strip comprises a continuous loop of base foil having pockets 1104a for containing medicament regularly spaced there along; and a strip oflid foil provided to the base foil to initially seal at least all of thepockets 1104 a. The two, end-located common index wheels 1105, 1106 arearranged for co-rotation (i.e. in the same direction) about respectiveaxles 1135, 1136 such that within the dispenser 1100 the two strips 1101a, 1101 b travel in a coupled sense.

Referring to FIG. 12 b, it may be seen that the strips 1101 a, 1101 bmay be arranged in fold-up configuration for receipt by the dispenser1100. Such configuration has the advantage of being extremely compact.

Referring now to FIG. 12 c, the dispenser 1100 may be seen to comprisefirst 1140 and second 1141 casing units rotatably coupled at pivot 1142to form a flip-out form casing readily movable between flipped open andclosed positions. The second casing unit 1141 is provided with outlet1124 for delivery of released powder form medicament to an orifice ofthe patient. In variations, the outlet 1124 is shaped as a mouthpiece oras a nozzle for receipt by the nasal cavity of a patient.

The dispenser 1100 is arranged to receive the medicament carrier strips1101 a, 1101 b, as shown. Thus, common index wheels 1105, 1106 arepivotally mounted for rotation within the respective first 1140 andsecond 1141 casing units such that the medicament carrier strips 1101 a,1101 b may be transported within the dispenser 1100. As shown in FIG. 12c, the dispenser 1100 is in the flipped open configuration, but whenclosed it will be appreciated that the strips 1101 a, 1101 b adopt thecompact, fold-up configuration as shown in FIG. 12 b.

The dispenser 1100 is also provided with means to index and accessmedicament from each blister strip 1101 a, 1101 b to enable the deliveryof a combination medicament product. Thus, each loop-form blister strip1101 a, 1101 b may be advanced by rotation of the common, multi-pocketindex wheels 1105, 1106 to bring successive pockets 1104 a thereoftowards a central opening station 1108. At the opening station 1108, thelid foil and base foil parts of each loop 1101 a, 1101 b are peelablyseparable about a peel surface (not visible). The resulting empty basefoil continues to be transported through the dispenser as the continuousloop form strip 1101 a, 1101 b is further advanced. The need for anydistinct base foil take-up chamber is thereby avoided.

The used lid foil feeds over the peel surface and is coiled aboutcommon, lid foil take-up spindle 1116 which rotates to wind up lid foil1120 a, 1120 b thereon. The lid take-up spindle 1116 is provided with acentrally located torsion spring 1117. The function of the torsionspring 1117 is to ensure a roughly constant driving tension is providedto each strip 1101 a, 1101 b by the common lid take-up spindle 1116 overthe course of each entire strip length. In particular, the torsionspring 1117 acts to compensate for the variation in drive tensionassociated with the increase in the effective winding diameter of commonlid take-up spindle 1116 as used lid foil 1120 a, 1120 b graduallybecomes wrapped there around. Thus, uniform indexing of each strip 1101a, 1101 b may be maintained over the entire loop form.

In use therefore, the dispenser 1100 is primed by drivably actuating theindex wheels 1105, 1106 to advance both blister strips 1101 a, 1101 b,thereby causing the leading pocket 1104 a, 1104 b thereof to be peeledopen. An appropriate ratchet mechanism may be employed to ensure that ineach actuating movement, each blister strip 1101 a, 1101 b is only movedsufficiently to open one pocket 1104 a, 1104 b thereof. To access thecontents of the opened pockets 1104 a, 1104 b, the patient then breathesin through the outlet 1124. This results in negative pressure beingtransmitted through suitable air channelling means (not visible) to theopened leading pocket 1104 a, 1104 b of each strip 1101 a, 1101 b at theopening station 1108. This in turn, results in the medicament powdercontained within each of the opened pockets 1104 a, 1104 b being drawnout through the air channelling means to the outlet 1124 and hence tothe patient as an inhaled combination medicament dose. It be appreciatedthat, mixing of each separately delivered component of the combinedmedicament product happens as the powder is transported from each openedpocket 1104 a, 1104 b to the outlet 1124.

In a variation herein, the dispenser 1100 is provided with means tosupply pressurized air to the open pockets 1104 a, 1104 b to assist inaerosolisation of the medicament powder contained therein. Such meansmay for example, comprise an air pump or an aerosol canister filled withcompressed air.

FIG. 13 shows a vane hub form lid driver 1216, which may be used in anyof the dispensers of FIGS. 2 to 12 c, as an alternative to the form oflid driver illustrated therein.

The lid driver 1216 comprises a rigid outer drum 1250 having a lateralindent 1252 for attachment of lid foil (not shown) provided thereto. Theinner wall 1254 of the drum 1250 is provided with multiple teeth 1255.Insert 1256 locates within the drum 1250 and defines spindle 1257 andvane arms 1258 a, 1258 b, the ends of which normally interact with teeth1255 on the inner wall 1254 of the drum 1250. The insert 1256 isrotatable relative to the drum 1256, but that rotation only occurs whensufficient rotational force is applied to the drum 1256 to overcome theinteraction of the teeth 1255 with the respective, resiliently flexiblevane arms 1258 a, 1258 b. The nature of this interaction thereforedefines a slipping (i.e. clutch) force, which must be overcome for freerotation of the insert 1256 relative to the drum 1250 to occur. In theabsence of the slipping force the drum 1250 and insert 1256 are fixedrelative to each other and rotatable as a single unit.

In use, the end of a lid foil of a peelable blister strip formmedicament carrier (e.g. as shown in FIG. 1) is attached to attachmentpoint 1252. The drum 1250 is then rotated to wind up lid foil thereonand to cause peeling open of the medicament carrier (e.g. as describedby reference to the earlier Figures). In more detail, the drum 1250 andinsert 1256 therein initially rotate as a single unit, lid foilgradually becomes wrapped around the drum 1250, and overall the liddriver 1216 provides driving force to peel lid foil from base foil ofthe medicament carrier. When that driving force exceeds a certain level(i.e. the slipping force) the interaction of the vane arms 1258 a, 1258b and the teeth 1255 result in slippage and the insert 1256 is caused torotate relative to the drum 1250, thereby preventing excess drivingforce from being transferred to the lid foil.

It will therefore be appreciated that the function of the insert 1256 isto prevent transfer of excess drive force to the lid foil by the drum1250 of the lid driver 1216. In particular, the slipping of insert 1256relative to drum 1250 once a slipping force is exceeded acts tocompensate for the variation in drive tension associated with theincrease in the effective winding diameter of common lid take-up spindle1216 as used lid foil gradually becomes wrapped around the drum 1250.Thus, uniform indexing of each strip may be maintained over the entirestrip length.

FIGS. 14 a to 14 c show side external views of a medicament dispenserherein with a movable cover 1340 at different stages of the cover driveaction. FIG. 15 shows a perspective view of the inner workings of themedicament dispenser of FIGS. 14 a to 14 c, which are actuable inresponse to movement of the cover 1340.

Movable cover 1340 is provided to the base unit 1300 and acts as thedrive mechanism for the parts of the dispensing mechanism and blisterstrips (not shown) contained there within. In the ‘at rest’ position, asshown in FIG. 14 a, the movable cover 1340 is positioned such as tocover mouthpiece 1324. It may be seen that the cover 1340 is movablealong track 1344 from ‘at rest’ (FIG. 14 a) to ‘primed’ (FIG. 14 b) to‘actuated’ (FIG. 14 c) positions. As will become clear from the detaileddescription below, such movement of the cover 1340 is coupled viagearing (not shown) to the strip advancement mechanism of the dispenserto prime and actuate the dispenser for the delivery of medicament.

Respective left and right chambers 1302 a, 1302 b of the base unit 1300are arranged for receipt of first and second medicament-containingblister strips (not shown, but having the form of the strip of FIG. 1).In use, each blister strip engages in its respective four pocket indexwheel 1306 a, 1306 b, and successive pockets are thereby guided towardsa central opening station 1308. At the opening station 1308, the lidfoil and base foil parts of each strip are peelably separable about beak1310 a, 1310 b. The resulting empty base foil coils wind up in a tightcoil on respective base take-up spools 1315 a, 1315 b, which rotate asshown.

Used lid foil feeds over its respective beak 1310 a, 1310 b and coilsabout respective lid take-up spindles 1316 a, 1316 b, which also rotateas shown to wind up lid foil thereon. Each lid take-up spindle 1316 a,1316 b is provided with a centrally located torsion spring 1317 a, 1317b. The function of the torsion spring 1317 a, 1317 b is to ensure aroughly constant driving tension is provided to each strip by its lidtake-up spindle 1316 a, 1316 b over the course of each entire striplength. In particular, each torsion spring 1317 a, 1317 b acts tocompensate for the variation in drive tension associated with theincrease in the effective winding diameter of each lid take-up spindle1316 a, 1316 b as used lid foil gradually becomes wrapped there around.Thus, uniform indexing of each strip is maintained over the entire striplength.

In use, the dispenser is actuated by the movement of movable cover 1340along track 1344 to drivably rotate the index wheels 1306 a, 1306 b andlid-take up spindles 1316 a, 1316 b to advance each blister strip. Themovement of the cover 1340 is coupled to that of the index wheels 1306a, 1306 b and lid-take up spindles 1316 a, 1316 b by suitable gearing(not visible). The gearing is arranged such that movement of the coverfrom the ‘at rest’ (FIG. 14 a) to ‘primed’ (FIG. 14 b) position does notitself result in any rotation of the index wheels 1306 a, 1306 b andlid-take up spindles 1316 a, 1316 b, but further movement to the‘actuated’ (FIG. 14 c) results in sufficient rotation to advance eachblister strip by one pocket distance.

Advancement of each strip causes the leading pocket thereof to be peeledopen and brought into communication with manifold 1322, which itselfcommunicates with mouthpiece 1324. Since the inner workings and blisterstrips of the dispenser 1300 are comprised within a sealed housing onlythe leading pockets of each strip communicate with manifold 1322 andthence to the outside environment via the mouthpiece 1324.

To access the medicament contents of the opened pockets of eachrespective blister strip the patient breathes in through the outlet1324. This results in air being drawn into the manifold 1322, and thatair being through manifold 1322 to the opened leading pocket of eachstrip at the opening station 1308. In turn, this results in themedicament powder contained within each of the opened pockets beingaerosolised and guided through the common manifold 1322 to the outlet1324 and hence to the patient as an inhaled combination medicament dose.

It may be appreciated that any of the parts of the dispenser or cassettethat contact the medicament suspension may be coated with materials suchas fluoropolymer materials (e.g. PTFE or FEP) which reduce the tendencyof medicament to adhere thereto. Any movable parts may also havecoatings applied thereto that enhance their desired movementcharacteristics. Frictional coatings may therefore be applied to enhancefrictional contact and lubricants (e.g. silicone oil) used to reducefrictional contact as necessary.

The medicament dispenser device of the invention is particularlysuitable for dispensing ‘multi-active’ medicament combinations,particularly for the treatment of respiratory disorders such as asthmaand chronic obstructive pulmonary disease (COPD), bronchitis and chestinfections.

The overall ‘multi-active’ combination product typically comprises incombination, a first medicament comprised within a first elongate formmedicament carrier; and at least one further medicament comprised withinat least one further elongate form medicament carrier. The medicamentdispenser device herein enables the delivery of these medicamentcomponents together in combination, even though on containment withinthe device they are contained within separate medicament carriers.

Appropriate medicaments may thus be selected from, for example,analgesics, e.g., codeine, dihydromorphine, ergotamine, fentanyl ormorphine; anginal preparations, e.g., diltiazem; antiallergics, e.g.,cromoglycate (e.g. as the sodium salt), ketobifen or nedocromil (e.g. asthe sodium salt); antiinfectives e.g., cephalosporins, penicillins,streptomycin, sulphonamides, tetracyclines and pentamidine;antihistamines, e.g., methapyrilene; anti-inflammatories, e.g.,beclomethasone (e.g. as the diproplonate ester), fluticasone (e.g. asthe propionate ester), flunisolide, budesonide, rofleponide, mometasonee.g. as the furoate ester), ciclesonide, triamcinolone (e.g. as theacetonide) or6α,9α-difluoro-11β-hydroxy-16α-methyl-3-oxo17α-propionyloxy-androsta-1,4-diene-17β-carbothioicacid S-(2-oxo-tetrahydro-furan-3-yl)ester; antitussives, e.g.,noscapine; bronchodilators, e.g., albuterol (e.g. as free base orsulphate), salmeterol (e.g. as xinafoate), ephedrine, adrenaline,fenoterol (e.g. as hydrobromide), formoterol (e.g. as fumarate),isoprenaline, metaproterenol, phenylephrine, phenylpropanolamine,pirbuterol (e.g. as acetate), reproterol (e.g. as hydrochloride),rimiterol, terbutaline (e.g. as sulphate), isoetharine, tulobuterol or4-hydroxy-7-[2-[[2-[[3-(2-phenylethoxy)propyl]sulfonyl]ethyl]amino]ethyl-2(3H)-benzothiazolone;adenosine 2a agonists, e.g.2R,3R,4S,5R)2-[6-Amino-2-(1S-hydroxymethyl-2-phenyl-ethylamino)-purin-9-yl]-5-(2-ethyl-2H-tetrazol-5-yl)-tetrahydro-furan-3,4-diol(e.g. as maleate); α₄ integrin inhibitors e.g.(2S)-3-[4-({[4-(aminocarbonyl)-1-piperidinyl]carbonyl}oxy)phenyl]-2-[((2S)-4-methyl-2-{[2-(2-methylphenoxy)acetyl]amino}pentanoyl)amino]propanoicacid (e.g. as free acid or potassium salt), diuretics, e.g., amiloride;anticholinergics, e.g., ipratropium (e.g. as bromide), tiotropium,atropine or oxitropium; hormones, e.g., cortisone, hydrocortisone orprednisolone; xanthines, e.g., aminophylline, choline theophyllinate,lysine theophyllinate or theophylline; therapeutic proteins andpeptides, e.g., insulin or glucagon; vaccines, diagnostics, and genetherapies. It will be clear to a person skilled in the art that, whereappropriate, the medicaments may be used in the form of salts, (e.g., asalkali metal or amine salts or as acid addition salts) or as esters(e.g., lower alkyl esters) or as solvates (e.g., hydrates) to optimisethe activity and/or stability of the medicament.

Suitable medicament components of the overall ‘multi-active’ combinationproduct are typically selected from the group consisting ofanti-inflammatory agents (for example a corticosteroid or an NSAID),anticholinergic agents (for example, an M₁, M₂, M₁/M₂ or M₃ receptorantagonist), other β₂-adrenoreceptor agonists, antiinfective agents(e.g. an antibiotic or an antiviral), and antihistamines. All suitablecombinations are envisaged.

Suitable anti-inflammatory agents include corticosteroids and NSAIDs.Suitable corticosteroids which may be used in combination with thecompounds of the invention are those oral and inhaled corticosteroidsand their pro-drugs which have anti-inflammatory activity. Examplesinclude methyl prednisolone, prednisolone, dexamethasone, fluticasonepropionate,6α,9α-difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioicacid S-fluoromethyl ester,6α,9α-difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-propionyloxy-androsta-1,4-diene-17β-carbothioicacid S-(2-oxo-tetrahydro-furan-3S-yl)ester, beclomethasone esters (e.g.the 17-propionate ester or the 17,21-dipropionate ester), budesonide,flunisolide, mometasone esters (e.g. the furoate ester), triamcinoloneacetonide, rofleponide, ciclesonide, butixocort propionate, RPR-106541,and ST-126. Preferred corticosteroids include fluticasone propionate,6α,9α-difluoro-11β-hydroxy-16α-methyl-17α-[(4-methyl-1,3-thiazole-5-carbonyl)oxy]-3-oxo-androsta-1,4-diene-17β-carbothioicacid S-fluoromethyl ester and6α,9α-difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioicacid S-fluoromethyl ester, more preferably6α,9α-difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioicacid S-fluoromethyl ester.

Suitable NSAIDs include sodium cromoglycate, nedocromil sodium,phosphodiesterase (PDE) inhibitors (e.g. theophylline, PDE4 inhibitorsor mixed PDE3/PDE4 inhibitors), leukotriene antagonists, inhibitors ofleukotriene synthesis, INOS inhibitors, tryptase and elastaseinhibitors, beta-2 integrin antagonists and adenosine receptor agonistsor antagonists (e.g. adenosine 2a agonists), cytokine antagonists (e.g.chemokine antagonists) or inhibitors of cytokine synthesis. Suitableother β₂-adrenoreceptor agonists include salmeterol (e.g. as thexinafoate), salbutamol (e.g. as the sulphate or the free base),formoterol (e.g. as the fumarate), fenoterol or terbutaline and saltsthereof.

Of particular interest is use of the compound of formula (I) incombination with a phosphodiesterase 4 (PDE4) inhibitor or a mixedPDE3/PDE4 inhibitor. The PDE4-specific inhibitor useful in this aspectof the invention may be any compound that is known to inhibit the PDE4enzyme or which is discovered to act as a PDE4 inhibitor, and which areonly PDE4 inhibitors, not compounds which inhibit other members of thePDE family as well as PDE4. Generally it is preferred to use a PDE4inhibitor which has an IC₅₀ ratio of about 0.1 or greater as regards theIC₅₀ for the PDE4 catalytic form which binds rolipram with a highaffinity divided by the IC₅₀ for the form which binds rolipram with alow affinity. For the purposes of this disclosure, the cAMP catalyticsite which binds R and S rolipram with a low affinity is denominated the“low affinity” binding site (LPDE 4) and the other form of thiscatalytic site which binds rolipram with a high affinity is denominatedthe “high affinity” binding site (HPDE 4). This term “HPDE4” should notbe confused with the term “hPDE4” which is used to denote human PDE4.

A method for determining IC₅₀s ratios is set out in U.S. Pat. No.5,998,428 which is incorporated herein in full by reference as thoughset out herein. See also PCT application WO 00/51599 for an anotherdescription of said assay.

Suitable PDE4 inhibitors include those compounds which have a salutarytherapeutic ratio, i.e., compounds which preferentially inhibit cAMPcatalytic activity where the enzyme is in the form that binds rolipramwith a low affinity, thereby reducing the side effects which apparentlyare linked to inhibiting the form which binds rolipram with a highaffinity. Another way to state this is that the preferred compounds willhave an IC₅₀ ratio of about 0.1 or greater as regards the IC₅₀ for thePDE4 catalytic form which binds rolipram with a high affinity divided bythe IC₅₀ for the form which binds rolipram with a low affinity.

A further refinement of this standard is that of one wherein the PDE4inhibitor has an IC₅₀ ratio of about 0.1 or greater; said ratio is theratio of the IC₅₀ value for competing with the binding of 1 nM of[³H]R-rolipram to a form of PDE4 which binds rolipram with a highaffinity over the IC₅₀ value for inhibiting the PDE4 catalytic activityof a form which binds rolipram with a low affinity using 1 μM[³H]-cAMPas the substrate.

Most suitable are those PDE4 inhibitors which have an IC₅₀ ratio ofgreater than 0.5, and particularly those compounds having a ratio ofgreater than 1.0. Preferred compounds are cis4-cyano-4-(3-cyclopentyloxy-4-methoxyphenyl)cyclohexan-1-carboxylicacid,2-carbomethoxy-4-cyano-4-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)cyclohexan-1-oneandcis-[4-cyano-4-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)cyclohexan-1-ol];these are examples of compounds which bind preferentially to the lowaffinity binding site and which have an IC₅₀ ratio of 0.1 or greater.

Other suitable medicament compounds include:cis-4-cyano-4-[3-(cyclopentyloxy)-4-methoxyphenyl]cyclohexane-1-carboxylicacid (also known as cilomalast) disclosed in U.S. Pat. No. 5,552,438 andits salts, esters, pro-drugs or physical forms; AWD-12-281 from elbion(Hofgen, N. et al. 15th EFMC Int Symp Med Chem (September 6-10,Edinburgh) 1998, Abst P.98; CAS reference No. 247584020-9); a9-benzyladenine derivative nominated NCS-613 (INSERM); D4418 fromChiroscience and Schering-Plough; a benzodiazepine PDE4 inhibitoridentified as Cl-1018 (PD-168787) and attributed to Pfizer; abenzodioxole derivative disclosed by Kyowa Hakko in WO99/16766; K-34from Kyowa Hakko; V-11294A from Napp (Landells, L. J. et al. Eur Resp J[Annu Cong Eur Resp Soc (September 19-23, Geneva) 1998] 1998, 12 (Suppl.28): Abst P2393); roflumilast (CAS reference No 162401-32-3) and apthalazinone (WO99/47505, the disclosure of which is hereby incorporatedby reference) from Byk-Gulden; Pumafentrine,(−)-p-[(4aR*,10bS*)-9-ethoxy-1,2,3,4,4a,10b-hexahydro-8-methoxy-2-methylbenzo[c][1,6]naphthyridin-6-yl]-N,N-diisopropylbenzamidewhich is a mixed PDE3/PDE4 inhibitor which has been prepared andpublished on by Byk-Gulden, now Aitana; arofylline under development byAlmirall-Prodesfarma; VM554/UM565 from Vernalis; or T-440 (TanabeSeiyaku; Fuji, K. et al. J Pharmacol Exp Ther, 1998, 284(1): 162), andT2585.

Suitable anticholinergic agents are those compounds that act asantagonists at the muscarinic receptor, in particular those compounds,which are antagonists of the M₁ and M₂ receptors. Exemplary compoundsinclude the alkaloids of the belladonna plants as illustrated by thelikes of atropine, scopolamine, homatropine, hyoscyamine; thesecompounds are normally administered as a salt, being tertiary amines.

Particularly suitable anticholinergics include ipratropium (e.g. as thebromide), sold under the name Atrovent, oxitropium (e.g. as the bromide)and tiotropium (e.g. as the bromide) (CAS-139404-48-1). Also of interestare: methantheline (CAS-53-46-3), propantheline bromide (CAS-50-34-9),anisotropine methyl bromide or Valpin 50 (CAS-80-50-2), clidiniumbromide (Quarzan, CAS-3485-62-9), copyrrolate (Robinul), isopropamideiodide (CAS-71-81-8), mepenzolate bromide (U.S. Pat. No. 2,918,408),tridihexethyl chloride (Pathilone, CAS-4310-35-4), and hexocycliummethylsulfate (Tral, CAS-115-63-9). See also cyclopentolatehydrochloride (CAS-5870-29-1), tropicamide (CAS-1508-75-4),trihexyphenidyl hydrochloride (CAS-144-11-6), pirenzepine(CAS-29868-97-1), telenzepine (CAS-80880-90-9), AF-DX 116, ormethoctramine, and the compounds disclosed in WO01/04118.

Suitable antihistamines (also referred to as H₁-receptor antagonists)include any one or more of the numerous antagonists known which inhibitH₁-receptors, and are safe for human use. All are reversible,competitive inhibitors of the interaction of histamine withH₁-receptors. Examples include ethanolamines, ethylenediamines, andalkylamines. In addition, other first generation antihistamines includethose which can be characterized as based on piperizine andphenothiazines. Second generation antagonists, which are non-sedating,have a similar structure-activity relationship in that they retain thecore ethylene group (the alkylamines) or mimic the tertiary amine groupwith piperizine or piperidine. Exemplary antagonists are as follows:

Ethanolamines: carbinoxamine maleate, clemastine fumarate,diphenylhydramine hydrochloride, and dimenhydrinate.

Ethylenediamines: pyrilamine amleate, tripelennamine HCl, andtripelennamine citrate.

Alkylamines: chlropheniramine and its salts such as the maleate salt,and acrivastine.

Piperazines: hydroxyzine HCl, hydroxyzine pamoate, cyclizine HCl,cyclizine lactate, meclizine HCl, and cetirizine HCl.

Piperidines: Astemizole, levocabastine HCl, loratadine or itsdescarboethoxy analogue, and terfenadine and fexofenadine hydrochlorideor another pharmaceutically acceptable salt.

Azelastine hydrochloride is yet another H₁ receptor antagonist which maybe used in combination with a PDE4 inhibitor.

Particularly suitable anti-histamines include methapyrilene andloratadine.

Co-formulation compatibility is generally determined on an experimentalbasis by known methods and may depend on chosen type of medicamentdispenser action.

The at least three active medicament components are suitably selectedfrom the group consisting of anti-inflammatory agents (for example acorticosteroid or an NSAID), anticholinergic agents (for example, an M₁,M₂, M₁/M₂ or M₃ receptor antagonist), other β₂-radrenoreceptor agonists,antiinfective agents (e.g. an antibiotic or an antiviral), andantihistamines. All suitable combinations are envisaged.

Suitably, the co-formulation compatible components comprise aβ₂-adrenoreceptor agonist and a corticosteroid; and the co-formulationincompatible component comprises a PDE-4 inhibitor, an anti-cholinergicor a mixture thereof. The β₂-adrenoreceptor agonists may for example besalbutamol (e.g., as the free base or the sulphate salt) or salmeterol(e.g., as the xinafoate salt) or formoterol (eg as the fumarate salt).The corticosteroid may for example, be a beclomethasone ester (e.g., thediproplonate) or a fluticasone ester (e.g., the propionate) orbudesonide.

In one example, the co-formulation compatible components comprisefluticasone propionate and salmeterol, or a salt thereof (particularlythe xinafoate salt) and the co-formulation incompatible componentcomprises a PDE-4 inhibitor, an anti-cholinergic (e.g. ipratropiumbromide or tiotropium bromide) or a mixture thereof.

In another example, the co-formulation compatible components comprisebudesonide and formoterol (e.g. as the fumarate salt) and theco-formulation incompatible component comprises a PDE-4 inhibitor, ananti-cholinergic (e.g. ipratropium bromide or tiotropium bromide) or amixture thereof.

Generally, powdered medicament particles suitable for delivery to thebronchial or alveolar region of the lung have an aerodynamic diameter ofless than 10 micrometers, preferably less than 6 micrometers. Othersized particles may be used if delivery to other portions of therespiratory tract is desired, such as the nasal cavity, mouth or throat.The medicament may be delivered as pure drug, but more appropriately, itis preferred that medicaments are delivered together with excipients(carriers) which are suitable for inhalation. Suitable excipientsinclude organic excipients such as polysaccharides (i.e. starch,cellulose and the like), lactose, glucose, mannitol, amino acids, andmaltodextrins, and inorganic excipients such as calcium carbonate orsodium chloride. Lactose is a preferred excipient.

Particles of powdered medicament and/or excipient may be produced byconventional techniques, for example by micronisation, milling orsieving. Additionally, medicament and/or excipient powders may beengineered with particular densities, size ranges, or characteristics.Particles may comprise active agents, surfactants, wall formingmaterials, or other components considered desirable by those of ordinaryskill.

The excipient may be included with the medicament via well-knownmethods, such as by admixing, co-precipitating and the like. Blends ofexcipients and drugs are typically formulated to allow the precisemetering and dispersion of the blend into doses. A standard blend, forexample, contains 13000 micrograms lactose mixed with 50 microgramsdrug, yielding an excipient to drug ratio of 260:1. Dosage blends withexcipient to drug ratios of from 100:1 to 1:1 may be used. At very lowratios of excipient to drug, however, the drug dose reproducibility maybecome more variable.

The medicament dispenser device of the invention is in one aspectsuitable for dispensing medicament for the treatment of respiratorydisorders such as disorders of the lungs and bronchial tracts includingasthma and chronic obstructive pulmonary disorder (COPD). In anotheraspect, the invention is suitable for dispensing medicament for thetreatment of a condition requiring treatment by the systemic circulationof medicament, for example migraine, diabetes, pain relief e.g. inhaledmorphine.

Accordingly, there is provided the use of a device according to theinvention for the treatment of a respiratory disorder, such as asthmaand COPD. Alternatively, the present invention provides a method oftreating a respiratory disorder such as, for example, asthma and COPD,which comprises administration by inhalation of an effective amount ofmedicament product as herein described from a device of the presentinvention.

The amount of any particular medicament compound or a pharmaceuticallyacceptable salt, solvate or physiologically functional derivativethereof which is required to achieve a therapeutic effect will, ofcourse, vary with the particular compound, the route of administration,the subject under treatment, and the particular disorder or diseasebeing treated. The medicaments for treatment of respiratory disordersherein may for example, be administered by inhalation at a dose of from0.0005 mg to 10 mg, preferably 0.005 mg to 0.5 mg. The dose range foradult humans is generally from 0.0005 mg to 100 mg per day andpreferably 0.01 mg to 1 mg per day.

It will be understood that the present disclosure is for the purpose ofillustration only and the invention extends to modifications, variationsand improvements thereto.

The application of which this description and claims form part may beused as a basis for priority in respect of any subsequent application.The claims of such subsequent application may be directed to any featureor combination of features described therein. They may take the form ofproduct, method or use claims and may include, by way of example andwithout limitation, one or more of the following claims:

1. A medicament dispenser for containing plural elongate form medicamentcarriers, each medicament carrier having multiple distinct medicamentdose portions carried thereby, said dispenser having a housing, andwithin said housing a dispensing mechanism for dispensing the distinctmedicament dose portions carried by each of said plural medicamentcarriers, said mechanism comprising, a) at least one receiving stationfor receiving each of the plural medicament carriers; b) a release forreleasing in combination a distinct medicament dose portion from each ofthe plural medicament carriers on receipt thereof by said receivingstation; c) an outlet, positioned to be in communication with thedistinct medicament dose portions releasable by said release; and d) atleast one indexer for individually indexing the distinct medicament doseportions of each of the plural medicament carriers, wherein saiddispenser further comprises a movable cover for the outlet, wherein thecover: is movable from an at rest position, in which the cover coversthe outlet, to a primed position and then an actuated position touncover the outlet, and couples to the dispensing mechanism such that:movement of said cover from the primed position to the actuated positionactuates one or more components of the dispensing mechanism, andmovement of said cover from the at rest position to the primed positiondoes not actuate said one or more components of the dispensingmechanism.
 2. A medicament dispenser according to claim 1, wherein themovable cover couples to said release and said at least one indexer foractuation thereof.
 3. A medicament dispenser according to claim 1,wherein said movable cover is coupled to the dispensing mechanism bygearing.
 4. A medicament dispenser according to claim 1, furthercomprising a track along which the movable cover is movable from the atrest position, to the primed position and then to the actuated position.5. A medicament dispenser according to claim 4, wherein the track is onthe housing.
 6. A medicament dispenser according to claim 1, wherein themovable cover is mounted to the housing for arcuate movement relativethereto from the at rest position, to the primed position and then tothe actuated position.
 7. A medicament dispenser according to claim 1,wherein the at least one indexer is comprised of an index wheel for eachmedicament carrier.
 8. A medicament dispenser according to claim 1,wherein the release is comprised of a take-up spindle for eachmedicament carrier.
 9. A medicament dispenser according to claim 1 forcontaining plural blister strip form medicament carriers, eachmedicament carrier having multiple distinct pockets for containingmedicament dose portions, wherein said pockets are spaced along thelength of and defined between two peelable sheets secured to each other,said dispensing mechanism comprising, a) an opening station forreceiving a pocket of each of said medicament carriers; and b) at leastone peeler positioned to engage a base sheet and a lid sheet of a pocketwhich has been received in said opening station for peeling apart such abase sheet and lid sheet, to open such a pocket; and wherein the outletis positioned to be in communication with an opened pocket and throughwhich a user can access a medicament dose portion from such an openedpocket; and the at least one indexer is for individually indexing thedistinct pockets of each of the plural medicament carriers.
 10. Amedicament dispenser according to claim 9, wherein for each blisterstrip the dispensing mechanism comprises a lid take-up spindle forwinding up the used lid sheet of the blister strip thereon and an indexwheel for indexing the blister strips and wherein the movable cover iscoupled to the dispensing mechanism such that movement of the movablecover from the at rest position to the primed position does not resultin any rotation of the lid takeup spindles and index wheels, but furthermovement of the movable cover to the actuated position results insufficient rotation of the lid take-up spindles and index wheels toadvance each blister strip by one pocket distance and the leading pocketthereof to be peeled open and brought into communication with theoutlet.
 11. A medicament dispenser according to claim 1 containing theplural elongate form medicament carriers.
 12. A medicament dispenseraccording to claim 11, wherein the dose portions of each medicamentcarrier are in powder form.
 13. A medicament dispenser according toclaim 1 which is an inhalation device with the outlet in the form of amouthpiece.
 14. A medicament dispenser for containing plural elongateblister strip form medicament carriers, each medicament carrier havingmultiple distinct medicament dose portions carried in multiple distinctpockets which are spaced along the length of and defined betweenpeelable base and lid sheets secured to each other, said dispenserhaving a housing, and within said housing a dispensing mechanism fordispensing the distinct medicament dose portions carried by each of saidplural medicament carriers, said mechanism comprising, at least onereceiving station for receiving each of the plural medicament carriers;an opening station for receiving a pocket of each of said medicamentcarriers; a release for releasing in combination a distinct medicamentdose portion from each of the plural medicament carriers on receiptthereof by said receiving station, comprising: at least one peelerpositioned to engage a base sheet and a lid sheet of a pocket which hasbeen received in said opening station for peeling apart such a basesheet and lid sheet, to open such a pocket; a lid take-up spindle foreach medicament carrier for winding up the lid sheet thereon; an outlet,positioned to be in communication with the distinct medicament doseportions releasable by said release and through which a user can accessa medicament dose portion from an opened pocket; and an index wheel foreach medicament carrier for individually indexing the distinct pocketsof each of the plural medicament carriers; wherein said dispenserfurther comprises a movable cover that couples to the dispensingmechanism and that is movable from an at rest position, in which thecover covers the outlet, to a primed position and then an actuatedposition to uncover the outlet, and movement of the movable cover iscoupled to the index wheels and lid take-up spindles by gearing that isarranged such that movement of the cover from the at rest position tothe primed position does not result in any rotation of the index wheelsand lid take-up spindles, but further movement of the cover to theactuated position results in sufficient rotation of the index wheels andlid take-up spindles to advance each medicament carrier by one pocketdistance.
 15. A medicament dispenser according to claim 14, wherein thedose portions of each medicament carrier are in powder form.
 16. Amedicament dispenser according to claim 14 which is an inhalation devicewith the outlet in the form of a mouthpiece.